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Galectin-3

Galectin-3 is a β-galactoside-binding lectin and the sole member of the chimera-type galectin subfamily, encoded by the LGALS3 gene located on human chromosome 14q21–22.^[1] This multifunctional protein, with a molecular weight of approximately 30 kDa and comprising 250 amino acids, features a modular structure including a C-terminal carbohydrate recognition domain (CRD) that binds β-galactosides such as N-acetyllactosamine, and a flexible N-terminal domain with tandem repeats (e.g., Pro-Gly-Ala-Tyr-Pro-Gly) that facilitates oligomerization and interactions with glycoproteins and glycolipids.^[2] Expressed ubiquitously in adult tissues—particularly in epithelial cells, macrophages, and immune cells—and secreted via non-classical exocytosis, galectin-3 plays pivotal roles in cellular processes like cell–cell and cell–matrix adhesion, proliferation, differentiation, apoptosis, pre-mRNA splicing, and inflammation.^[1] In physiological contexts, galectin-3 contributes to tissue homeostasis, wound healing, and innate immune responses by acting as both a pattern-recognition receptor (PRR) for microbial structures (e.g., lipopolysaccharides and fungal oligomannans) and a damage-associated molecular pattern (DAMP) that amplifies inflammation.^[2] It promotes phagocytosis, neutrophil recruitment, and macrophage polarization toward an M2 anti-inflammatory phenotype, aiding in pathogen defense and tissue repair, such as during corneal re-epithelialization or resolution of pneumonia.^[2] During embryogenesis, its expression is tissue-specific, supporting developmental processes like cell migration and immune cell activation.^[1] Pathologically, galectin-3 is implicated in a wide array of diseases due to its pleiotropic effects, often promoting fibrosis, tumor progression, and chronic inflammation.^[1] In cancer, it is overexpressed in malignancies such as breast, colorectal, and thyroid tumors, enhancing metastasis through lattice formation on cell surfaces that modulates adhesion and signaling.^[1] It drives fibrotic remodeling in organs like the liver (e.g., in non-alcoholic steatohepatitis), kidneys, and lungs, and is elevated in cardiovascular conditions including heart failure and atherosclerosis, where it correlates with left ventricular dysfunction and poor prognosis.^[1] Additionally, galectin-3 serves as a prognostic biomarker in sepsis, systemic sclerosis, and type 2 diabetes, with serum levels reflecting disease severity and guiding therapeutic strategies.^[1] Galectin-3 is also emerging as a therapeutic target, with inhibitors under investigation in clinical trials for fibrosis, cancer, and other inflammatory diseases as of 2025.^[3]

Discovery and nomenclature

Historical identification

Galectin-3 was first identified in 1982 as Mac-2, a novel 32-kDa cell surface antigen specific to a subpopulation of thioglycollate-elicited mouse peritoneal macrophages, by Ho and Springer using monoclonal antibodies. This discovery highlighted its expression on activated macrophages, distinguishing it from other differentiation antigens like Mac-1. Early characterization revealed Mac-2's role in immune responses, as it was induced by specific differentiative signals in mononuclear phagocytes. In the mid-1980s, the same protein was independently recognized under different names in various cell types. The Barondes laboratory identified it as carbohydrate-binding protein 35 (CBP35), a 35-kDa β-galactoside-binding lectin abundant in the nuclear and cytoplasmic compartments of mouse 3T3 fibroblasts, with potential involvement in cell proliferation and adhesion. Concurrently, in 1986, Leffler and Barondes described L-29 as a soluble lactose-binding lectin from rat lung epithelium and fibroblasts, demonstrating its affinity for β-galactosides and cooperative binding to glycoconjugates, which linked it to cell-matrix interactions. These identifications preceded the unified understanding of galectin-3, with initial studies emphasizing its lectin activity in pre-galectin nomenclature. Further investigations in the late 1980s and early 1990s connected these aliases through biochemical and immunological analyses, revealing Mac-2/CBP35/L-29 as the same entity involved in cell adhesion, IgE binding, and laminin interactions in immune and epithelial contexts.^[4] The Barondes group played a pivotal role in elucidating its β-galactoside specificity during this period, establishing foundational links to cellular processes like phagocytosis and inflammation. The galectin family nomenclature, formalizing it as galectin-3, was introduced in 1994 to resolve these disparate names based on discovery order.^[5]

Gene and family classification

Galectin-3 is encoded by the LGALS3 gene, located on the long arm of human chromosome 14 at locus 14q22.3. The gene spans approximately 27 kb (26,671 bp) and consists of six exons separated by five introns.^[6] This protein belongs to the galectin family, a group of 15 soluble β-galactoside-binding lectins in humans, classified into three structural subtypes: prototype galectins (non-covalent homodimers with a single carbohydrate-recognition domain, such as galectin-1), tandem-repeat galectins (with two carbohydrate-recognition domains linked by a peptide, such as galectin-9), and chimeric galectins (featuring a unique fusion of a carbohydrate-recognition domain with a distinct N-terminal domain).^[7] Galectin-3 is the sole chimeric member of this family. The galectin family exhibits an ancient evolutionary history, with orthologs identified in diverse taxa including sponges, fungi, invertebrates, and vertebrates; galectin-3 itself appears to have arisen specifically within vertebrate lineages through gene duplication and divergence events.^[8] In 1994, the Galectin Nomenclature Committee formalized the naming convention for these proteins, assigning sequential numbers based on their discovery order while emphasizing their shared β-galactoside-binding properties. Historically, galectin-3 has been referred to by synonyms such as Mac-2 (originally identifying its role as a macrophage antigen) and GALBP (galactoside-binding protein), terms that aid in distinguishing it from other family members like the prototype galectin-1.^[9]

Structure

Domain architecture

Galectin-3 exhibits a chimeric architecture unique among the galectin family, consisting of 250 amino acids in humans with a molecular weight of approximately 30 kDa.^[10] The protein comprises an N-terminal non-lectin domain (NTD) of about 110 residues and a C-terminal carbohydrate recognition domain (CRD) of roughly 130 residues.^[10] This modular design enables diverse interactions, with the NTD featuring a flexible, intrinsically disordered region rich in proline and glycine residues.^[11] The NTD includes 9 collagen-like repeats of the Pro-Gly-Ala-Tyr-Pro-Gly-XXX motif (where X represents variable residues), which facilitate oligomerization and multivalency upon ligand binding.^[12] These repeats promote the formation of higher-order assemblies, such as pentamers, observed in crystal structures of NTD-containing variants.^[12] In contrast, the CRD forms a compact β-sandwich fold typical of galectins, harboring conserved motifs essential for β-galactoside recognition, including HxNPR and WGxEE sequences that coordinate ligand binding through hydrogen bonding and hydrophobic interactions.^[13] As a mature protein, Galectin-3 lacks a classical signal peptide, permitting its localization in the nucleus, cytoplasm, and extracellular space via non-conventional secretion pathways.^[14] Crystal structures of the CRD reveal its structural integrity in both apo and ligand-bound states; for instance, the apo form (PDB: 3ZSM) displays an open binding groove at 1.25 Å resolution, while the lactose-bound complex (PDB: 1A3K) at 2.1 Å resolution highlights conserved water molecules and residue rearrangements upon ligand engagement.^[15]^[16] These structures also demonstrate how NTD interactions can drive pentameric or oligomeric assemblies, underscoring the protein's capacity for lattice formation.

Biochemical properties

Galectin-3 undergoes specific post-translational modifications that influence its localization and function. Phosphorylation occurs at serine 6 (Ser6) in the N-terminal domain, catalyzed by casein kinase 1 (CK1), which acts as a molecular switch promoting nuclear export and enhancing anti-apoptotic activity.^[17] Casein kinase 2 (CK2) can also phosphorylate galectin-3, contributing to regulatory signaling.^[18] Despite its role as a β-galactoside-binding lectin, galectin-3 exhibits limited glycosylation, with no definitive experimental evidence of significant N- or O-linked modifications, though predictive models suggest potential sites.^[19] The protein demonstrates notable stability and folding characteristics. As a calcium-independent lectin, galectin-3 maintains its carbohydrate-binding affinity without requiring divalent cations, distinguishing it from C-type lectins.^[20] Its isoelectric point (pI) is approximately 8.5, rendering it soluble at neutral physiological pH. The N-terminal domain (NTD) contributes to resistance against proteolysis, though the protein can be cleaved at specific sites under certain conditions, preserving core functionality.^[21] Oligomerization of galectin-3 is mediated by the intrinsically disordered NTD, enabling self-association into trimers or higher-order oligomers at elevated concentrations, which facilitates multivalent interactions and lattice formation on glycan arrays.^[11] Spectroscopic analyses reveal the carbohydrate recognition domain (CRD) of galectin-3 to be dominated by β-sheet secondary structure, as evidenced by far-UV circular dichroism (CD) spectra showing characteristic minima around 217 nm. Galectin-3 lacks enzymatic activity, functioning solely as a non-catalytic binding protein.^[22]

Expression and regulation

Tissue and cellular distribution

Galectin-3 displays ubiquitous expression in various tissues and cell types under normal physiological conditions, with particularly high levels observed in epithelial cells of the intestine, kidney, and lung, as well as in immune cells including macrophages, monocytes, dendritic cells, eosinophils, mast cells, and activated T and B lymphocytes, and in fibroblasts and endothelial cells.^[23]^[24] Its expression is notably lower in the brain and skeletal muscle compared to these sites. Galectin-3 is absent from mature erythrocytes, though it appears in erythroid precursors during erythropoiesis.^[25] At the subcellular level, galectin-3 is primarily localized in the cytoplasm, where it constitutes the majority of the protein pool, with additional distribution to the nucleus and extracellular space via a non-classical secretion pathway that bypasses the endoplasmic reticulum-Golgi apparatus.^[23]^[24] During development, galectin-3 expression is upregulated in embryonic tissues, neural structures such as the notochord, and epithelia lining the respiratory and digestive systems, with patterns first detectable around embryonic day 8.5 in mice and persisting through organogenesis.^[26]^[24] These expression profiles are highly conserved across species, showing similar distributions in rodent models like mice and rats.^[24] In immune cells, baseline expression can be modulated by cytokines such as interferon-γ.^[27]

Factors influencing expression

The expression of Galectin-3, encoded by the LGALS3 gene, is primarily regulated at the transcriptional level through specific elements in its promoter region. The human LGALS3 promoter contains multiple regulatory motifs, including AP-1 binding sites and NF-κB sites, which facilitate activation in response to inflammatory signals.^[28] These elements allow for rapid induction of transcription during stress or immune activation. Additionally, the promoter features GC boxes that serve as binding sites for Sp1 transcription factors, contributing to basal and inducible expression across various cell types.^[29] Several cytokines and stimuli upregulate Galectin-3 transcription via these promoter elements, particularly in inflammatory contexts. For instance, lipopolysaccharide (LPS), a component of bacterial cell walls, induces Galectin-3 expression in monocyte-like THP-1 cells, with mRNA levels rising up to 6.3-fold after 24 hours of exposure at 100 ng/mL, accompanied by a 45-65% increase in protein levels over 72 hours.^[30] Similarly, transforming growth factor-β (TGF-β) modulates Galectin-3 expression through Smad signaling, though the direction varies by cell type; in nucleus pulposus cells, TGF-β suppresses expression via Smad3 binding to nine sites in the proximal promoter, reducing mRNA and protein levels within 24 hours.^[31] Epigenetic mechanisms further fine-tune Galectin-3 expression, often leading to silencing in pathological states. Hypermethylation of CpG islands in the LGALS3 promoter is associated with gene silencing in early-stage prostate cancer, where stage II tumors exhibit heavy methylation compared to lighter methylation in advanced stages III and IV, correlating with reduced expression.^[32] Post-transcriptional repression occurs through microRNAs, such as miR-128, which directly targets the 3' untranslated region of LGALS3 mRNA, downregulating Galectin-3 protein levels in colorectal cancer cells; miR-128 downregulation in tumors inversely correlates with elevated Galectin-3 and poorer prognosis.^[33] Hormonal and environmental factors also influence Galectin-3 levels. Estrogen, specifically estradiol, upregulates Galectin-3 expression in human endometrial cells, reducing apoptosis and supporting tissue remodeling, with effects observed alongside progesterone in proliferative phases.^[34] In tumor microenvironments, hypoxia induces Galectin-3 via hypoxia-inducible factor-1α (HIF-1α), which binds to hypoxia response elements in the promoter; this leads to increased transcription in renal carcinoma and breast cancer cells under low-oxygen conditions, enhancing cell survival and migration.^[35]^[36] Feedback mechanisms involving Galectin-3 itself contribute to regulatory loops. The protein interacts with Sp1 to modulate transcription of target genes, and given the presence of Sp1 binding sites in the LGALS3 promoter, this suggests potential auto-regulatory control, as seen in its enhancement of cyclin D1 promoter activity through Sp1 in breast epithelial cells.^[37] Species-specific differences exist in promoter architecture; while both human and rodent LGALS3 promoters contain conserved elements like Runx2 binding sites, variations in CpG island density and response element positioning affect inducibility, with rodent promoters showing distinct regulation in stress responses compared to human counterparts.^[38]

Biological functions

Ligand binding and interactions

Galectin-3 primarily recognizes and binds to β-galactoside-containing glycans, such as lactose and N-acetyllactosamine, through its carbohydrate recognition domain (CRD). The binding affinity for these monosaccharides or disaccharides is typically modest, with dissociation constants (Kd) in the range of 100–1000 μM for lactose (Kd ≈ 1 mM) and approximately 200 μM for N-acetyllactosamine.^[39] This interaction involves a network of hydrogen bonds between the galactosyl hydroxyl groups and key CRD residues, including histidine 158, arginine 144, and asparagine 165, which stabilize the ligand in a shallow binding groove.^[39] The affinity of Galectin-3 for β-galactosides is significantly enhanced by multivalency, where clustered glycan presentations on glycoproteins or cell surfaces lead to avidity effects, reducing effective Kd values to the nanomolar range. For instance, binding to multivalent substrates like asialofetuin demonstrates positive cooperativity, allowing Galectin-3 to form stable complexes that promote lattice assembly.^[40] This multivalent enhancement is crucial for physiological interactions, as single glycan units alone exhibit low-affinity binding insufficient for functional outcomes.^[41] Beyond glycans, Galectin-3 engages in protein-protein interactions, both extracellularly and intracellularly. Extracellularly, it binds to integrins such as α5β1, facilitating cell-matrix adhesion and processes like angiogenesis through glycan-mediated cross-linking.^[42] It also interacts with CD98, a heterodimeric glycoprotein, promoting its dimerization and downstream signaling in immune cells and placental trophoblasts.^[43] Additionally, Galectin-3 associates with BP180 (collagen XVII) in epidermal contexts, contributing to skin integrity via adhesive interactions.^[44] Intracellularly, Galectin-3 binds to anti-apoptotic proteins like Bcl-2, modulating its function through the conserved NWGR motif, and to activated K-Ras-GTP, stabilizing oncogenic signaling.^[45]^[46] A hallmark of Galectin-3 function is its ability to form glycan lattices on cell surfaces by cross-linking N-glycosylated glycoproteins, creating dynamic microdomains that compartmentalize receptors and modulate their diffusion and endocytosis. These lattices arise from the multivalent binding of Galectin-3 to β-galactoside-terminated glycans on multiple glycoproteins, such as integrins and growth factor receptors, resulting in clustered signaling platforms.^[47] The formation of these microdomains is reversible and sensitive to glycan branching, with hyperbranched N-glycans promoting stable lattice assembly.^[48] Binding interactions of Galectin-3 have been characterized using techniques like isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), which reveal cooperative effects in multivalent contexts and modest enthalpic contributions from single-ligand binding. For example, ITC measurements confirm that lactose binding is enthalpically driven with negative entropy, while SPR assays demonstrate enhanced on-rates for multivalent glycans.^[49] Inhibition studies often employ thiodigalactoside, a non-hydrolyzable analog that competitively blocks the CRD with a Ki in the micromolar range, disrupting lattice formation and protein interactions.^[49] These assays underscore the role of the CRD in both glycan and protein recognition, with brief structural insights showing a preorganized binding site for β-galactosides.^[50]

Roles in cellular processes

Galectin-3 plays a key role in cell adhesion and migration by forming extracellular lattices that regulate integrin clustering, thereby facilitating processes such as wound healing and angiogenesis. Specifically, galectin-3 binds to integrin α5β1 on epithelial cells, promoting their migration during skin wound repair through phase separation mechanisms that enhance cell-matrix interactions.^[51] In angiogenesis, galectin-3 supports endothelial cell migration and tube formation by interacting with integrins like αvβ3, contributing to vascular remodeling in physiological contexts.^[52] These functions rely on galectin-3's carbohydrate recognition domain binding to glycosylated ligands on cell surfaces and extracellular matrix components.^[53] Intracellularly, galectin-3 participates in signaling pathways, particularly through its nuclear export, which modulates apoptosis and transcription. Phosphorylated galectin-3 is exported from the nucleus via CRM1-dependent mechanisms, allowing it to interact with anti-apoptotic proteins like Bcl-2 in the cytoplasm, thereby suppressing caspase activation and promoting cell survival during stress responses.^[17] In the nucleus, galectin-3 acts as a co-activator for transcription factors such as Sp1, enhancing promoter activity for genes like cyclin D1 and p21, which regulate cell cycle progression.^[37]^[54] In immune cells, galectin-3 modulates macrophage function by promoting phagocytosis and cytokine release, essential for innate immune responses. It enhances the uptake of apoptotic cells and pathogens in macrophages through intracellular interactions that stabilize phagocytic cups and activate downstream signaling like PI3K/Akt.^[55] Additionally, galectin-3 supports alternative macrophage activation induced by IL-4, leading to increased expression of anti-inflammatory cytokines such as IL-10 and TGF-β, which aid in tissue repair and resolution of inflammation.^[56] Galectin-3 also contributes to pre-mRNA splicing in the nucleus by binding to heterogeneous nuclear ribonucleoproteins (hnRNPs), such as hnRNPA2B1, within splicing factor-enriched subnuclear speckles. This interaction facilitates the assembly of the spliceosome and promotes efficient constitutive splicing of pre-mRNAs, ensuring proper mRNA maturation for cellular homeostasis.^[57]^[58]

Pathological roles

Fibrosis

Galectin-3 is upregulated in response to transforming growth factor-β (TGF-β), a key profibrotic cytokine, which enhances its expression in fibroblasts and macrophages during fibrotic remodeling.^[59] This upregulation promotes myofibroblast differentiation by stabilizing β-catenin signaling, leading to increased extracellular matrix (ECM) deposition, including collagens I and III.^[60] In animal models of fibrosis, genetic knockout of Galectin-3 significantly attenuates these processes, reducing myofibroblast activation and collagen accumulation across multiple organs.^[59] In the liver, Galectin-3 contributes to fibrosis progression in non-alcoholic steatohepatitis (NASH) and cirrhosis by activating hepatic stellate cells and promoting ECM synthesis.^[61] Studies in Galectin-3-deficient mice fed high-fat diets demonstrate reduced inflammation, hepatocyte injury, and fibrotic scarring compared to wild-type controls.^[62] Similarly, in idiopathic pulmonary fibrosis (IPF), Galectin-3 drives fibroblast-to-myofibroblast transition and lung ECM remodeling, with inhibition preventing β-catenin-mediated TGF-β activation in bleomycin-induced models.^[60] Knockout models show decreased collagen deposition and improved lung architecture post-injury.^[60] In chronic kidney disease (CKD), macrophage-derived Galectin-3 exacerbates renal fibrosis by amplifying TGF-β1 signaling and oxidative stress via Nox4 interaction, leading to tubular atrophy and interstitial ECM buildup.^[63] Galectin-3 ablation in normotensive rat models of renal injury reduces fibrotic markers and preserves tubular integrity.^[64] Recent investigations have also implicated Galectin-3 in post-wound skin fibrosis, where its increased expression in dermal fibroblasts correlates with excessive scarring and delayed healing in murine excisional wound models.^[65] Early associations between Galectin-3 and fibrosis emerged in the 1990s through studies identifying its role in macrophage activation and ECM interactions during tissue repair.^[66] More recent work from 2023 onward has highlighted Galectin-3 inhibition's potential to limit cardiac fibrosis post-myocardial infarction, with targeted blockers impeding progressive collagen remodeling and heart failure development in rodent models.^[67] Serum Galectin-3 levels have been shown to correlate with overall fibrosis severity scores, such as the Enhanced Liver Fibrosis (ELF) test, in patients with advanced liver disease.^[68]

Cardiovascular disease

Galectin-3 plays a significant role in the pathogenesis of cardiovascular diseases, particularly through its promotion of inflammation, fibrosis, and adverse remodeling in cardiac and vascular tissues. Elevated levels of galectin-3 are associated with increased risk of heart failure, where it predicts myocardial remodeling and mortality. In patients with heart failure with reduced ejection fraction (HFrEF), plasma galectin-3 concentrations exceeding 17.8 ng/mL are indicative of poor prognosis, correlating with higher rates of hospitalization and death.^[69] This threshold has been validated in large cohorts, such as those from the CORONA and COACH trials, where changes in galectin-3 levels over time further stratified risk, with persistent elevations signaling progressive deterioration. In atherosclerosis, galectin-3, also known as Mac-2, facilitates monocyte adhesion to endothelial cells and contributes to plaque instability by enhancing macrophage infiltration and oxidative stress within lesions (with roles that may be context-dependent). It binds to cell surface glycoconjugates on monocytes, promoting their recruitment and activation, which accelerates atheroma formation and vulnerability to rupture.^[70] Inhibition of galectin-3 in apolipoprotein E-deficient mouse models has demonstrated reduced plaque progression and lesion size, underscoring its pro-atherogenic effects.^[71] Recent studies as of 2025 highlight galectin-3's prognostic value in patients undergoing percutaneous coronary intervention (PCI), where elevated serum levels independently predict major adverse cardiovascular events, including restenosis and thrombosis post-procedure with drug-eluting stents.^[72] Furthermore, galectin-3 synergizes with aldosterone in hypertension-induced cardiac hypertrophy, amplifying inflammatory signaling and fibroblast activation that drive left ventricular remodeling.^[73] Blockade of galectin-3 in aldosterone-exposed models attenuates hypertrophy and preserves cardiac function, suggesting a mechanistic link between mineralocorticoid excess and galectin-3-mediated pathology.^[74] At the cellular level, galectin-3 induces cardiomyocyte apoptosis via activation of stress pathways, including caspase-3 and mitochondrial dysfunction, while simultaneously promoting fibrosis through extracellular matrix deposition by cardiac fibroblasts.^[75] In mouse models of myocardial infarction, galectin-3 knockout (Gal3-/-) animals exhibit reduced infarct size, decreased macrophage infiltration, and improved post-ischemic healing compared to wild-type counterparts, indicating galectin-3's contribution to adverse remodeling.^[76] These effects overlap with fibrotic processes in the heart, where galectin-3 exacerbates scar formation following injury.^[77]

Cancer

Galectin-3 (Gal-3) plays a prominent pro-oncogenic role in tumor biology by facilitating neoplastic transformation, progression, and metastasis across various malignancies. Overexpressed in approximately 70% of solid tumors, including breast, colon, and pancreatic cancers, Gal-3 contributes to aggressive phenotypes by modulating key signaling pathways and cellular interactions.^[78] Its carbohydrate recognition domain (CRD) binds β-galactoside-containing glycans on cell surface receptors, thereby influencing adhesion, migration, and survival signals that drive oncogenesis.^[79] In the tumor microenvironment, Gal-3 promotes immune evasion and immunosuppression by recruiting tumor-associated macrophages (TAMs) and forming glycan-based barriers that shield cancer cells from immune surveillance. Secreted Gal-3 interacts with glycan ligands on immune cells, such as T cells and natural killer cells, inhibiting their activation and cytotoxic functions while enhancing the infiltration of pro-tumorigenic M2-like TAMs via chemokine axes like CCL2-CCR2.^[80] This remodeling fosters a permissive niche for tumor growth and metastasis. Additionally, Gal-3 briefly supports angiogenic processes in tumors by inducing endothelial cell proliferation and vascular permeability, further sustaining the hypoxic microenvironment.^[81] Gal-3 enhances metastatic progression primarily through resistance to anoikis—a form of programmed cell death triggered by detachment from the extracellular matrix—and induction of epithelial-mesenchymal transition (EMT). In breast and colon cancers, Gal-3 stabilizes integrin signaling and upregulates anti-apoptotic proteins like Bcl-2, enabling circulating tumor cells to survive in suspension and colonize distant sites.^[82] Mechanistically, extracellular Gal-3 binds to mucin 1 (MUC1) and integrins (e.g., αvβ3), promoting cell invasion by clustering these receptors and activating downstream pathways like PI3K/Akt that facilitate matrix metalloproteinase secretion and extracellular matrix degradation.^[83] Intracellularly, nuclear Gal-3 translocates to the nucleus, where it binds β-catenin and activates Wnt/β-catenin signaling, leading to transcription of pro-metastatic genes such as cyclin D1 and MMP7 in colon and other epithelial cancers.^[84] Recent research as of 2025 highlights Gal-3's involvement in extracellular vesicle (EV) glycosylation, which aids cancer dissemination. Cancer-derived EVs enriched in Gal-3 binding proteins (e.g., LGALS3BP) exhibit altered N-glycan and sialic acid patterns that enhance tumor cell adhesion to endothelial surfaces and promote pre-metastatic niche formation in distant organs like the lungs and liver.^[85] These advances underscore Gal-3's therapeutic potential in blocking metastatic cascades.^[86]

Inflammation and other conditions

Galectin-3 exhibits a dual role in inflammation, promoting acute responses while also facilitating resolution in certain contexts. In acute inflammation, such as sepsis, galectin-3 acts as an alarmin that augments the inflammatory cascade by functioning as an endogenous ligand for Toll-like receptor 4 (TLR4), thereby enhancing cytokine production and immune cell activation in response to bacterial infections like Francisella novicida.^[87] Conversely, during the resolution phase of inflammation, galectin-3 promotes anti-inflammatory effects, including the induction of eosinophil apoptosis in allergic conditions, which helps dampen prolonged immune responses.^[88] In chronic inflammation, galectin-3 sustains immune activation by modulating cytokine release and immune cell recruitment, contributing to persistent tissue damage across various inflammatory states.^[89] In autoimmune diseases, galectin-3 predominantly exerts pro-inflammatory effects. In rheumatoid arthritis, galectin-3 is upregulated in synovial tissues, where it drives cytokine and chemokine production, exacerbating joint destruction through NF-κB activation in fibroblasts and immune cells.^[90] Similarly, in inflammatory bowel disease (IBD), galectin-3 amplifies the induction phase of acute colitis by activating the NLRP3 inflammasome and promoting pro-inflammatory cytokine secretion, as evidenced by reduced disease severity in galectin-3 knockout mice subjected to dextran sulfate sodium-induced colitis models.^[91] These findings highlight galectin-3's contribution to autoimmune pathogenesis, though its role can vary by disease stage and tissue context.^[92] Beyond inflammation and autoimmunity, galectin-3 influences several other conditions. In aging-related processes, galectin-3 serves as a marker of cellular senescence and is implicated in metabolic disorders, where its elevated expression correlates with insulin resistance and tissue dysfunction in obesity and diabetes, as noted in recent reviews.^[93] Neurologically, galectin-3 associates with Alzheimer's disease pathology, where it is elevated in cerebrospinal fluid and promotes amyloid-β oligomerization and plaque formation, intensifying microglial activation around deposits.^[94] In wound healing, galectin-3 facilitates angiogenesis by binding integrin α5β1, enhancing endothelial cell motility and vascular remodeling essential for tissue repair.^[51] Emerging research underscores galectin-3's relevance in additional disorders. As of 2025, galectin-3 has been identified as a novel biomarker for glycogen storage disease type III (GSD III), reflecting muscle impairments due to its upregulation in affected skeletal tissues.^[95] In viral infections, galectin-3 contributes to the cytokine storm in severe COVID-19 by amplifying pro-inflammatory signaling and immune hyperactivation, with higher serum levels predicting disease severity and poor outcomes.^[96]

Clinical applications

Biomarker utility

Galectin-3 serves as a prognostic and diagnostic biomarker across multiple pathologies, particularly those involving fibrosis, due to its measurable elevation in serum and plasma reflecting disease severity. It is quantified primarily via enzyme-linked immunosorbent assays (ELISA), including the FDA-cleared BG Galectin-3 test developed by BG Medicine, which detects levels in human serum or plasma with high sensitivity.^[97] This assay demonstrates excellent stability, with samples remaining viable for up to 48 hours at ambient temperature post-centrifugation, up to 15 days at 2–8°C or 22–28°C, and indefinitely when frozen at −20°C or −70°C.^[98]^[99] In heart failure (HF), Galectin-3 facilitates risk stratification, with levels exceeding 17.8 ng/mL—based on the assay's FDA labeling—indicating heightened risk of mortality, hospitalization, and disease progression.^[100] For chronic kidney disease (CKD), higher Galectin-3 concentrations correlate with accelerated progression and tubulointerstitial fibrosis, offering utility in monitoring renal decline and identifying high-risk patients for early intervention.^[101] In oncology, particularly glioblastoma, Galectin-3 overexpression in tumor tissue and serum signifies advanced staging, aggressive malignancy, and reduced survival, supporting its role in prognostic staging.^[102] As of 2025, emerging data highlight Galectin-3's predictive power for post-percutaneous coronary intervention (PCI) outcomes, where elevated levels independently forecast major adverse cardiovascular events in patients receiving drug-eluting stents.^[72] Combining Galectin-3 with NT-proBNP improves accuracy in forecasting cardiovascular events and HF incidence in stable coronary artery disease, enhancing risk models for revascularized patients.^[103] In liver fibrosis, Galectin-3 is gaining traction as a non-invasive marker, with serum levels rising proportionally to cirrhosis severity (e.g., 25.9 ng/mL in compensated vs. 81 ng/mL in decompensated cases), positioning it as a potential alternative or complement to the Enhanced Liver Fibrosis (ELF) panel for assessing progression in metabolic dysfunction-associated steatotic liver disease.^[104] Despite its strengths, Galectin-3 interpretation is limited by renal clearance dynamics, as impaired kidney function elevates circulating levels independently of primary pathology, requiring eGFR adjustments for accurate prognostic assessment.^[105] It exhibits no significant circadian variation, ensuring consistent measurements across sampling times, though transient post-exercise increases (resolving within 1–3 hours) may warrant controlled conditions in active patients.^[106]

Therapeutic development

Therapeutic development for galectin-3 (Gal-3) focuses on inhibiting its pathological functions in fibrosis, cancer, and inflammation through targeted small molecules, natural compounds, and biologics. Early efforts emphasized carbohydrate-based inhibitors that bind the carbohydrate recognition domain (CRD) to block ligand interactions, while more recent advances explore non-carbohydrate scaffolds and alternative mechanisms to enhance selectivity and efficacy. Preclinical and clinical studies have demonstrated potential in reducing fibrosis progression and tumor growth, though translation to approved therapies remains ongoing due to specificity challenges. Small-molecule inhibitors represent a primary class, with GB1211, a synthetic Gal-3 antagonist, advancing in Phase I/II trials for advanced liver fibrosis since 2022, showing safety and preliminary antifibrotic effects in patients with compensated cirrhosis. Natural inhibitors like modified citrus pectin (MCP), a galactoside-rich polysaccharide, have exhibited Gal-3 blockade in preclinical models of hypertension, atherosclerosis, and bladder cancer, reducing monocyte adhesion and tumor proliferation by disrupting extracellular Gal-3 signaling. Antibody-based approaches include monoclonal antibodies targeting Gal-3, though inhaled small-molecule mimics like TD139 (also known as GB0139), a thiodigalactoside derivative, demonstrated tolerability and Gal-3 inhibition in early Phase II trials for idiopathic pulmonary fibrosis (IPF); however, the subsequent Phase 2b GALACTIC-1 trial failed to meet its primary efficacy endpoint in 2023, leading to discontinuation of development.^[107] Recent innovations include non-carbohydrate small molecules such as K2 and L2, identified in 2025, which potently inhibit Gal-3 binding to ligands like thrombospondin-1 in cancer models without affecting other galectins. Therapeutic strategies target distinct domains: CRD blockers, such as TD139 and belapectin (GR-MD02), prevent carbohydrate-mediated interactions essential for extracellular matrix remodeling and immune modulation. N-terminal domain (NTD) disruptors aim to interfere with Gal-3 oligomerization and intracellular signaling, as the NTD facilitates multimerization that amplifies pro-fibrotic effects in preclinical cardiac and hepatic models. Gene silencing via small interfering RNA (siRNA) has shown promise in preclinical settings, downregulating Gal-3 expression to suppress proinflammatory cytokines like IL-6 and IL-1β in monocyte-derived dendritic cells stimulated by Toll-like receptors. Clinical trials highlight mixed progress, with belapectin, a galactoarabino-rhamnogalacturonate polysaccharide, discontinued in 2021 for nonalcoholic steatohepatitis (NASH)-associated cancer due to lack of efficacy but continuing in the Phase 2b/3 NAVIGATE trial for NASH cirrhosis, where 2025 interim results indicated reduced portal hypertension and fibrosis biomarkers in compensated patients. Analogs and next-generation inhibitors, guided by quantitative structure-activity relationship (QSAR) modeling in 2025 studies, emphasize improved CRD selectivity to minimize cross-reactivity with Gal-1 or Gal-7. Biomarker-guided patient selection, using serum Gal-3 levels, has been integrated in trials like NAVIGATE to enrich for high-risk cohorts. Key challenges include off-target effects, as many inhibitors bind homologous galectins, potentially disrupting physiological roles in immune homeostasis, and delivery barriers for intracellular Gal-3 functions, where poor cell penetration limits efficacy against nuclear or cytoplasmic activities in cancer and neurodegeneration. Ongoing research prioritizes highly selective, orally bioavailable agents to address these hurdles.

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They are found in all metazoans examined, from sponges and fungi, to both invertebrates and vertebrates. As many as 15 galectins have been identified to ...
[8]
LGALS3 - Galectin-3 - Homo sapiens (Human) | UniProtKB | UniProt
Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration.
[9]
The Two Endocytic Pathways Mediated by the Carbohydrate ...
Dec 26, 2012 · Human Gal-3 is composed of 250 amino acids, with the NT comprising approximately 110 amino acids at the N-terminus and the CRD approximately 130 ...
[10]
The intrinsically disordered N-terminal domain of galectin-3 ... - NIH
We show that the disordered N-terminal domain (residues ∼20–100) interacts with itself and with a part of the CRD not involved in carbohydrate recognition (β- ...Missing: architecture | Show results with:architecture
[11]
Crystallization of a human galectin-3 variant with two ordered ...
Jun 29, 2018 · The NTS and the nine repeats form the N-terminal tail (NT). In full-length Gal-3, it is connected to the C-terminal CRD that harbors two sites ...
[12]
Identification of galectin-9 and its antibacterial function in Yellow ...
Aug 21, 2025 · The HxNPR and WGxEE motifs play a crucial role in β-galactoside binding and are highly conserved among galectin-9 proteins across different ...
[13]
Nuclear transport of galectin-3 and its therapeutic implications - PMC
In this review we have summarized the dynamics of galectin-3 shuttling between the nucleus and the cytoplasm, the nuclear transport mechanisms of galectin-3.
[14]
3ZSM: Crystal structure of Apo Human Galectin-3 CRD at 1.25 ...
Dec 14, 2011 · Crystal structure of Apo Human Galectin-3 CRD at 1.25 angstrom resolution, at room temperature. PDB DOI: https://doi.org/10.2210/pdb3ZSM/pdb.
[15]
1A3K: X-RAY CRYSTAL STRUCTURE OF THE HUMAN GALECTIN ...
Jul 15, 1998 · We report here the x-ray crystal structure of the human galectin-3 CRD, in complex with lactose and N-acetyllactosamine, at 2.1-A resolution.Missing: 2LLH | Show results with:2LLH
[16]
Nuclear Export of Phosphorylated Galectin-3 Regulates Its ... - NIH
Gal-3 undergoes posttranslational modification by addition of a phosphate group catalyzed by CK1, and its phosphorylation serves as a molecular switch for ...
[17]
important post-translational modifications of galectin-3 - PubMed
... post-translational modifications of galectin-3, including cleavage and phosphorylation. Cleavage of galectin-3 by MMPs, PSA, and proteases from parasites ...Missing: Ser6 CK1 CK2
[18]
Lectin affinity chromatography and quantitative proteomic analysis ...
Oct 5, 2020 · Although, thus far, there has been no experimental report whether Galectin-3 is glycosylated, however, based on artificial neural networks, the ...
[19]
Modified Citrus Pectin Reduces Galectin-3 Expression and Disease ...
Galectins are low molecular weight, calcium-independent, β-galactoside-binding lectins [1]. Galectin-3 is a multi-domain molecule which includes an N ...
[20]
Galectin-3 Is Associated with the Plasma Membrane of Lens Fiber ...
A cluster of three protein spots with an apparent molecular weight of 31,000 and isoelectric points ranging between 7 and 8.5 were resolved and identified as ...Missing: calcium- | Show results with:calcium-
[21]
Biophysical and Structural Characterization of the Interaction ... - NIH
... galectin-3 (Gal3) and the LPS from Pseudomonas aeruginosa. This manuscript ... circular dichroism; spectrofluorimetry; dynamic and static light ...
[22]
https://pmc.ncbi.nlm.nih.gov/articles/PMC10932368/
[23]
https://doi.org/10.3892/ijmm.2017.3311
[24]
Galectin-3 regulates erythropoiesis and enhances the ... - NIH
Mar 22, 2025 · Our findings emphasize the critical role of Gal-3 in modulating erythropoiesis and suggest that Gal-3+ CECs possess enhanced immunoregulatory capacities.
[25]
Galectin-3 is expressed in the notochord, developing bones, and ...
In the embryo proper, galectin-3 message and protein are first detected in notochord, starting from 8.5 days post coitum (dpc), and persist until this structure ...
[26]
https://pubmed.ncbi.nlm.nih.gov/7655085/
[27]
Examination of the regulation of galectin-3 expression in cancer
Besides, several regulatory elements such as GC box, CRE motif, AP-1 site, and NF-κB sites, the promoter of galectin-3 gene (LGALS3) contains several CpG ...
[28]
Overexpression of Galectin-1 and Galectin-3 in hepatocellular ...
The overexpression of Gal-1 and Gal-3 correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, and poor prognosis.
[29]
Galectin-3 expression in response to LPS, immunomodulatory drugs ...
Aug 7, 2025 · In this study, we show that lipopolysaccharide (LPS) provokes upregulation of galectin-3 expression on both gene and protein level in monocyte- ...
[30]
TGFβ Regulates Galectin-3 Expression through Canonical Smad3 ...
These studies suggest that TGFβ, through Smad3 controls Galectin-3 expression in NP cells and may have implications in the intervertebral disc degeneration.Missing: LPS | Show results with:LPS
[31]
A GALECTIN-3-DEPENDENT PATHWAY UPREGULATES ... - NIH
Here we show that the production of IL-6 in BMMSC is in part stimulated by galectin-3 binding protein (Gal-3BP) secreted by neuroblastoma cells.
[32]
Evidence of Heavy Methylation in the Galectin 3 Promoter in Early ...
The gal3 promoter in stage II prostate adenocarcinoma (PCa) was found heavily methylated, whereas in stages III and IV, it was only lightly methylated.
[33]
Posttranscriptional regulation of Galectin-3 by miR-128 contributes ...
We found that miR-128 level was frequently down-regulated in CRC and negatively correlated with Galectin-3 level.Missing: epigenetic hypermethylation
[34]
HIF-1 alpha is a regulator of galectin-3 expression in the ... - PubMed
Our studies indicate that HIF-1 alpha regulates galectin-3 expression by interacting with hypoxia regulatory elements in the promoter region.Missing: estrogen endometrium
[35]
Galectin-3 Up-Regulation in Hypoxic and Nutrient Deprived ...
Nov 4, 2014 · Gal-3 is a key factor in tumor growth and engraftment in hypoxic and nutrient-deprived microenvironments.
[36]
Galectin-3 Enhances Cyclin D(1) Promoter Activity Through SP1 and ...
We found that galectin-3 induces cyclin D(1) promoter activity in human breast epithelial cells independent of cell adhesion through multiple cis-elements.Missing: auto- rodent
[37]
Expression of Galectin-3 in Skeletal Tissues Is Controlled by Runx2
Here we show that in vitro, galectin-3 expression is up-regulated in the preosteoblastic cell line MC3T3-E1 during the matrix maturation stage of the osteoblast ...<|separator|>
[38]
X-ray Crystal Structure of the Human Galectin-3 Carbohydrate ...
an N- and C-terminal CRD linked in tandem by a short polypeptide segment (18). The galectin-3 CRD shows sequence identity ranging from 30–40% with galectins ...Missing: architecture | Show results with:architecture
[39]
Identification of Galectin-3 As a High-Affinity Binding Protein for ...
Sep 1, 1995 · The cDNA and the protein product have been characterized by several laboratories, reporting it as a 35-kD carbohydrate-binding protein (CBP35), ...
[40]
Galectin-3 Binding to α5β1 Integrin in Pore Suspended Biomembranes
Our study demonstrates the capacity of WTGal3 to oligomerize in a cargo protein-dependent manner at low nanomolar concentrations.
[41]
Membrane trafficking of CD98 and its ligand galectin 3 in BeWo cells ...
Apr 20, 2007 · We used the high affinity of galectin 3 for lactose (Lac) to inhibit binding between the glycosylated sites of CD98 and galectin 3 CDR domains, ...
[42]
Diminished Expression of Galectin-3 Around Blisters in Bullous ...
In this study, we evaluated galectin-3 expression in BP as a first step in assessing its role in the pathogenesis of this autoimmune blistering process.
[43]
Galectin-3 leads to attenuation of apoptosis through Bax ... - NIH
With the respect to a binding motif, Gal-3 has unique aspartate-tryptophan-glycine-arginine (NWGR), shown as a conservative motif of the Bcl-2 family, and its ...
[44]
Galectin-3 Regulates a Molecular Switch from N-Ras to K-Ras ...
Aug 15, 2005 · Galectin-3 (Gal-3), a pleiotropic carbohydrate-binding protein, is a selective binding partner of activated K-Ras-GTP.
[45]
Galectin–glycan lattices regulate cell-surface glycoprotein ... - NIH
Galectin–glycan lattice formation is also involved in regulating the signalling threshold of some cell-surface glycoproteins, including T-cell receptors and ...
[46]
The galectin lattice at a glance | Journal of Cell Science
Jul 1, 2015 · The 15 mammalian galectins have either one or two conserved carbohydrate recognition domains (CRDs), with galectin-3 being able to pentamerize; ...The Galectin Lattice: A... · Galectin Lattice Composition · Cancer
[47]
Systematic Tuning of Fluoro-galectin-3 Interactions Provides ...
Dec 28, 2017 · To differentiate between these thiodigalactosides confirmation from a second binding assay, such as ITC, was required and is described below.
[48]
The Carbohydrate-Binding Site in Galectin-3 Is Preorganized ... - NIH
Here we report the high- to ultra-high-resolution crystal structures of the carbohydrate recognition domain of galectin-3 (Gal3C) in the ligand-free state.Missing: HxNPR WDxHxR
[49]
Galectin-3-integrin α5β1 phase separation disrupted by advanced ...
Aug 7, 2025 · Here, we demonstrate that galectin-3 promotes skin wound healing and angiogenesis via binding to its receptor integrin α5β1, and enhances ...
[50]
Galectin-3 is an important mediator of VEGF
Anti-αvβ3 integrin antibodies inhibit galectin-3–mediated angiogenesis. To determine whether αvβ3 integrin is involved in galectin-3–induced angiogenesis, HUVE ...
[51]
Interaction between Galectin-3 and Integrins Mediates Cell-Matrix ...
Our results further showed that the adhesion to substrate-bound Gal-3 is mediated, at least partially, by integrins α5β1 and αVβ3. These integrins are ...
[52]
Indispensable role of Galectin-3 in promoting quiescence of ... - Nature
Apr 9, 2021 · Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion.
[53]
Critical role of galectin-3 in phagocytosis by macrophages - PubMed
Galectin-3 may play an important role in both innate and adaptive immunity by contributing to phagocytic clearance of microorganisms and apoptotic cells.
[54]
Regulation of alternative macrophage activation by galectin-3
Feb 15, 2008 · IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, ...Missing: phagocytosis cytokine
[55]
Galectin-3 interacts with components of the nuclear ...
Jul 19, 2016 · Galectin-3 as well as hnRNPA2B1 co-localize in splicing factor enriched subnuclear speckles. Specific depletion of the two galectins, galectin-1 ...
[56]
Identification of galectin-3 as a factor in pre-mRNA splicing - NIH
Galectin-3 (M(r) approximately 35000) is a galactose/lactose-specific lectin found in association with ribonucleoprotein complexes in many animal cells.Missing: hnRNPs | Show results with:hnRNPs
[57]
Galectin-3 regulates myofibroblast activation and hepatic fibrosis
These data suggest that Galectin-3 is required for TGF-beta mediated myofibroblast activation and matrix production. Finally, in vivo siRNA knockdown of ...
[58]
Regulation of transforming growth factor-β1-driven lung fibrosis by ...
Mar 1, 2012 · This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel ...Missing: upregulated | Show results with:upregulated
[59]
Galectin-3 inhibition as a potential therapeutic target in ... - PubMed
Feb 27, 2023 · NASH represents a spectrum of disease that may lead to hepatic fibrosis and eventual cirrhosis, with the risk of cirrhosis decompensation, and ...
[60]
Galectin-3 ablation protects mice from diet-induced NASH
Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis.
[61]
Macrophage Derived Galectin-3 Promotes Renal Fibrosis ... - PubMed
Aug 13, 2025 · Macrophage-derived Gal3 is found to promote Transforming growth factor beta 1 (TGFβ1) signaling activation and renal fibrogenesis. Genetic ...
[62]
Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive ...
Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage.<|control11|><|separator|>
[63]
Increased Expression of Galectin-3 in Skin Fibrosis - PubMed
Dec 5, 2022 · This paper aims to ascertain whether the expression of GAL-3 is increased in relevant in vitro and in vivo models of skin fibrosis.
[64]
Galectin-3: A Harbinger of Reactive Oxygen Species, Fibrosis ... - NIH
Gal-3 expression, however, is not confined to macrophages, and it is found to be expressed in fibroblasts (where it was originally discovered), smooth muscle ...
[65]
Inhibition of galectin-3 post-infarction impedes progressive fibrosis ...
Nov 25, 2023 · Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.
[66]
Usefulness of Enhanced Liver Fibrosis, Glycosylation Isomer of Mac ...
liver fibrosis. Methods: ELF, M2BPGi, galectin-3 ... Enhanced Liver Fibrosis (ELF) test accurately identifies liver fibrosis in patients with chronic hepatitis C.
[67]
Prognostic value of changes in galectin-3 levels over time in patients ...
A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients.Missing: HFrEF | Show results with:HFrEF
[68]
Galectin-3 Identifies a Subset of Macrophages With a Potential ...
Apr 16, 2020 · Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis.
[69]
Galectin-3 Is an Amplifier of Inflammation in Atherosclerotic Plaque ...
In vitro, Gal-3 has been shown to bind to the cell surfaces of monocytes/ macrophages and cause superoxide release and Ca2+ influx. Gal-3 also induces the ...
[70]
Inhibition of galectin-3 reduces atherosclerosis in apolipoprotein E ...
We conclude that inhibiting galectin-3 causes decreased atherosclerosis. Strategies to inhibit galectin-3 function may reduce plaque progression.
[71]
Prognostic significance of serum galectin-3 in predicting ... - NIH
Jul 17, 2025 · Our data suggest that serum galectin-3 is an independent predictor of cardiovascular events in patients undergoing PCI with DES. Keywords: ...
[72]
Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in ...
These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as ...
[73]
The impact of galectin-3 inhibition on aldosterone-induced cardiac ...
This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction.
[74]
https://pubmed.ncbi.nlm.nih.gov/25458174/
[75]
Knockdown of Galectin-3 confers myocardial protection against ...
May 6, 2025 · Galectin-3 deficiency in mice led to reduced infarct size and improved cardiac function after I-R injury. This finding is consistent with ...Myocardial I-R Animal Model · Galectin-3 Enhances... · Anti-Galectin-3 Inhibits...Missing: knockout | Show results with:knockout
[76]
The Therapeutic Potential of Blocking Galectin-3 Expression in ...
May 3, 2018 · Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early ...
[77]
Roles of galectin‑3 in the tumor microenvironment and tumor ...
Sep 22, 2020 · The interaction of galectin-3 with endothelial CD146/MCAM in the circulation resulted in increased secretion of IL-6, granulocyte colony- ...
[78]
Extracellular Galectin-3 in Tumor Progression and Metastasis - PMC
Chimera galectins, in turn, consist of one CRD connected to a collagen-like sequence formed by Pro-Gly-Tyr tandem repeats and an N-terminal domain (Figure 1A).
[79]
Galectin-3 induces pathogenic immunosuppressive macrophages ...
Aug 13, 2024 · In vitro, galectin-3 impairs TREM2-mediated phagocytosis and promotes the conversion of TREM2+ macrophages to pro-tumoral M2-like TAMs.
[80]
Galectin-3 in angiogenesis and metastasis - PMC - PubMed Central
Galectin-3 plays a significant role in angiogenesis at the primary tumor site, migration and invasion into the surrounding tissue, emboli formation in the blood ...
[81]
Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed ...
Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry ...
[82]
Galectin-3 binds to MUC1-N-terminal domain and triggers ...
Yu et al. reported that recombinant galectin-3 interacts with the TF antigen expressed on MUC1-ND, facilitating the adhesion of epithelial cancer cells to the ...
[83]
Galectin-3 Mediates Nuclear β-Catenin Accumulation and Wnt ...
We demonstrated that galectin-3 up-regulates β-catenin expression and its nuclear accumulation and augments Wnt signaling in human colon cancer cells.
[84]
Altered glycosylation of EVs in cancers: galectin-3-binding protein ...
Jul 15, 2025 · Although MS is widely utilized, EVs glycome analysis experience several major drawbacks including a lack of suitable MS fragmentation methods, ...<|control11|><|separator|>
[85]
Investigating carbohydrate based ligands for galectin-3 with docking ...
The design of inhibitors targeting the carbohydrate recognition domain that is known to recognize galactose is an important approach in the fight against cancer ...
[86]
Targeting galectin-3 in cancer by novel and unique inhibitors of non ...
Sep 29, 2025 · The observation of conformation changes in Circular Dichroism analysis of galectin-3 β ... Using circular dichroism spectra to estimate protein ...
[87]
Galectin-3 Functions as an Alarmin: Pathogenic Role for Sepsis ...
These findings suggest that galectin-3 functions as an alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida ...
[88]
Galectin-3: its role in asthma and potential as an anti-inflammatory ...
Dec 9, 2013 · Gal-3 has been shown to be involved in many aspects in allergic inflammation, such as eosinophil recruitment, airway remodeling, development of a Th2 phenotype.
[89]
The regulation of inflammation by galectin-3 - PubMed
Galectin-3 can be viewed as a regulatory molecule acting at various stages along the continuum from acute inflammation to chronic inflammation and tissue ...Missing: auto- Sp1
[90]
Galectin 3 Induces a Distinctive Pattern of Cytokine and Chemokine ...
Galectin 3 induced secretion of interleukin-6 (IL-6), granulocyte–macrophage colony-stimulating factor, CXCL8, and MMP-3 in both synovial and skin fibroblasts.
[91]
Galectin-3 Plays an Important Pro-inflammatory Role in the Induction ...
Galectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: it plays an important role in autoimmune/inflammatory and ...Missing: rheumatoid arthritis knockout
[92]
Galectin-3 in autoimmunity and autoimmune diseases - PMC
Gal-3 seems to play a pro-inflammatory role in RA62 and high serum levels of gal-3 have been found in mice during collagen-induced arthritis.<|separator|>
[93]
Pleiotropic regulatory mechanisms and targeted therapeutic ...
Sep 22, 2025 · A structural study revealed that CRD of Gal-3 directly interacts with phosphorylated Tau, accelerating its conformational transition into β- ...Missing: enzymatic | Show results with:enzymatic
[94]
Galectin-3 is elevated in CSF and is associated with Aβ deposits ...
Jul 27, 2022 · Galectin-3 is elevated in CSF and is associated with Aβ deposits and tau aggregates in brain tissue in Alzheimer's disease.
[95]
Galectin-3: a novel biomarker of glycogen storage disease type III
Apr 14, 2025 · The main result of this study is the identification of GAL3 as a biomarker of the muscle impairments observed in GSDIII. GAL3 is a 29–35 kDa ...
[96]
Galectin-3 as an important prognostic marker for COVID-19 severity
Jan 26, 2023 · Significantly higher sera levels of PCT were noted in severe and critical group and might be marker of cytokine storm or multiple infections. As ...
[97]
[PDF] K093758.pdf - REVIEW MEMORANDUM - FDA
Test Principle: BGM Galectin-3 is a microtiter plate-based ELISA for the quantitative determination of galectin-3 levels in human serum and plasma.
[98]
Galectin-3, Serum | ARUP Laboratories Test Directory
Stability Acceptable times/temperatures for specimens. Times include storage and transport time to ARUP. After separation from cells: Ambient: 48 hours; ...
[99]
Galectin-3: A new biomarker for the diagnosis, analysis and ...
Samples can be stored for up to 15 days at either 22–28 °C or 2–8 °C before analysis; measurements are stable after storage at − 20 °C or −70 °C for at least 6 ...
[100]
Prognostic Value of Changes in Galectin-3 Levels Over Time in ...
To categorize patients, a threshold value of galectin-3 of 17.8 ng/mL was applied, based on the US Food and Drug Administration–cleared assay labeling for risk ...
[101]
Galectin-3 as a Next-Generation Biomarker for Detecting Early ...
Higher concentrations of Gal-3 may be associated with progression of CKD, indicating potential novel mechanisms related to Gal-3 expression that may contribute ...
[102]
Galectins in Glioma: Current Roles in Cancer Progression and ...
Nov 4, 2021 · A common finding with Gal-3 in GBM is that overexpression is associated with a poor prognosis and correlates with malignant potential [64,65,66] ...Missing: CKD | Show results with:CKD
[103]
Heart failure biomarkers in revascularized patients with stable ...
Sep 10, 2024 · Gal-3 and NT-proBNP could be used as an additional tool for diagnosis and severity assessment of stable obstructive coronary artery disease.
[104]
Comparison between galectin-3 and YKL-40 levels for the ...
Aug 7, 2025 · Galectin-3 levels increased significantly according to the severity of cirrhosis (25.9 ± 2.7; 57.4 ± 29.6; and 81 ± 27 ng/mL in Class A, B, and ...
[105]
Prognostic value of galectin-3, a novel marker of fibrosis, in patients ...
Galectin-3 is a recently developed biomarker associated with fibrosis and inflammation, and it may play a role in cardiac remodeling in HF. We determined its ...
[106]
Galectin-3 as a novel biomarker for disease diagnosis and a target ...
The serum levels of galectin-3 are associated with changes in the LV structure and function, indicating that galectin-3 may be involved in the process of LV ...