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Fibroblast growth factor 2

Fibroblast growth factor 2 (FGF2), also known as basic fibroblast growth factor (bFGF) or heparin-binding growth factor 2 (HBGF-2), is a multifunctional cytokine encoded by the FGF2 gene located on human chromosome 4q27–28.^[1]^[2] This protein belongs to the fibroblast growth factor (FGF) family, which comprises 22 structurally related members involved in diverse physiological processes.^[1] FGF2 is a potent mitogen and angiogenic factor that binds with high affinity to heparin and fibroblast growth factor receptors (FGFRs), primarily FGFR1 and FGFR2 IIIc isoforms, to regulate cell proliferation, differentiation, survival, and migration across multiple cell types, including endothelial cells, fibroblasts, and neural progenitors.^[1]^[3] FGF2 exists in multiple isoforms generated through alternative translation initiation from a single mRNA transcript with multiple CUG and AUG start codons, resulting in low molecular weight (LMW) forms—such as the canonical 18 kDa isoform—and high molecular weight (HMW) isoforms (22–34 kDa in humans).^[1] The LMW isoform is predominantly secreted and acts in paracrine/autocrine manners, while HMW isoforms are primarily nuclear and exert intracrine effects by modulating gene expression and chromatin remodeling.^[1] Secretion of FGF2 occurs via an unconventional, non-endoplasmic reticulum-Golgi pathway and is facilitated by heparan sulfate proteoglycans (HSPGs), which stabilize the protein and enhance its interaction with FGFRs to activate downstream signaling pathways, including MAPK/ERK, PI3K/Akt, and PLCγ.^[1] These isoforms exhibit context-dependent functions, with LMW FGF2 often promoting proliferation and HMW forms influencing differentiation or exerting protective roles.^[1] FGF2 plays essential roles in embryonic development, including limb bud formation, nervous system patterning, and vascularization as early as embryonic day 7.5 in mice.^[1] In adults, it contributes to wound healing, tissue repair, and maintenance of homeostasis in organs such as bone, heart, and brain, where it supports angiogenesis, neurogenesis, and extracellular matrix remodeling.^[1]^[2] Dysregulation of FGF2 is implicated in various pathologies; for instance, overexpression promotes tumor angiogenesis and metastasis in cancers like breast and melanoma, while deficiencies or imbalances contribute to osteoarthritis, diabetic nephropathy, and cardiomyopathy.^[1] Therapeutically, recombinant FGF2 has been explored for applications in regenerative medicine, including tympanic membrane repair and cardioprotection, highlighting its dual potential as a pro-growth and protective agent.^[1]

Discovery and Nomenclature

Discovery

Fibroblast growth factor 2 (FGF2) was first purified to homogeneity in 1975 from bovine pituitary glands by Denis Gospodarowicz and colleagues, who isolated approximately 5 mg of the protein per kg of tissue using a combination of chromatography techniques including ion-exchange and gel filtration.^[4] This mitogen was initially designated as a fibroblast growth factor based on its potent stimulation of DNA synthesis and proliferation in cultured BALB/c 3T3 fibroblasts at concentrations as low as 2 × 10^{-13} M.^[4] Subsequent characterization revealed its basic isoelectric point of approximately 9.6, leading to its renaming as basic fibroblast growth factor (bFGF) to distinguish it from the concurrently identified acidic FGF (FGF1). In the early 1980s, protein sequencing of the bovine bFGF provided its primary amino acid sequence, comprising 146 residues with a molecular weight of about 18 kDa, and highlighted its structural similarity to acidic FGF. The bovine cDNA was cloned in 1986, revealing a single open reading frame lacking a classical N-terminal signal peptide, which accounted for its non-conventional export from cells despite acting extracellularly. Cloning of the human FGF2 gene followed in 1986 via reverse translation of the protein sequence and screening of cDNA libraries, confirming 99% amino acid identity to the bovine form and establishing FGF2 as a conserved member of the emerging FGF family. Key advancements in the late 1980s and 1990s demonstrated that a single FGF2 mRNA transcript encodes multiple protein isoforms through alternative initiation of translation at upstream CUG codons, producing high molecular weight variants (21–34 kDa) in addition to the canonical 18 kDa low molecular weight form starting at an AUG codon. These isoforms were identified in various cell types, with the larger ones exhibiting distinct intracellular localization and functions. Early bioassays not only confirmed FGF2's mitogenic effects on fibroblasts but also revealed its strong proliferative activity on vascular endothelial cells, promoting angiogenesis in vitro at picomolar concentrations and underscoring its broader role in tissue growth and repair.^[5]

Alternative Names and Isoforms

Fibroblast growth factor 2 (FGF2) is known by several alternative names, including basic fibroblast growth factor (bFGF), heparin-binding growth factor-2 (HBGF-2), and FGF-β.^[6]^[3]^[7] FGF2 is translated from a single mRNA transcript into multiple isoforms via alternative initiation at upstream CUG codons and a canonical AUG start site.^[8]^[9] The four main isoforms in humans are the 18 kDa canonical form, initiated at the AUG codon and primarily cytoplasmic; the 22 kDa and 22.5 kDa forms, initiated at the first and second upstream CUG codons, respectively; and the 34 kDa form, initiated at a further upstream CUG codon, which features the longest N-terminal extension.^[8]^[10]^[9] The longer isoforms (22 kDa, 22.5 kDa, and 34 kDa) contain N-terminal extensions that include nuclear localization signals, directing them to the nucleus and influencing their intracellular activities, whereas the 18 kDa isoform lacks these signals and is predominantly cytoplasmic.^[11]^[1] Export mechanisms also differ: the 18 kDa isoform, which lacks a classical secretory signal peptide, relies on unconventional protein secretion pathways, while the high molecular weight isoforms exhibit distinct localization and export behaviors tied to their extended sequences.^[8]^[10] These isoform variants, including their translation initiation mechanisms and localization properties, are evolutionarily conserved across mammalian species.^[1]^[12]

Gene and Structure

Gene Location and Expression

The human FGF2 gene is located on chromosome 4q28.1 and spans approximately 71 kb of genomic DNA, consisting of three exons separated by two introns, with the coding sequence distributed across these exons but lacking introns within the core translated region for the primary isoform.^[2]^[13] The gene's promoter region is TATA-less and lacks a consensus CAAT box, relying instead on GC-rich sequences for basal transcription.^[14] Transcriptional regulation of FGF2 involves multiple factors, including AP-1 and Sp1 binding sites in the proximal promoter, which mediate responses to growth stimuli and stress, as well as hypoxia-inducible factors (HIF-1) that drive upregulation under low-oxygen conditions.^[15] Alternative translation initiation from canonical AUG or non-AUG (CUG) codons within the same mRNA transcript generates distinct isoforms, with CUG starts producing nuclear-localized high-molecular-weight forms.^[2] FGF2 exhibits ubiquitous expression across human tissues at low to moderate levels, with notably higher abundance in the brain (particularly in neurons and glial cells), retina, kidney, and placenta, where it supports developmental and homeostatic functions.^[16] Expression is dynamically upregulated in response to cellular injury, hypoxia, and inflammatory signals, such as those from cytokines or tissue damage, enhancing angiogenic and reparative processes.^[17] Post-transcriptional control of FGF2 mRNA stability is mediated by AU-rich elements (AREs) in the unusually long 3' untranslated region (UTR), which promote rapid decay under normal conditions but allow stabilization during stress to fine-tune protein levels. Species-specific differences in isoform expression are evident, with rodents showing a higher prevalence of the 18 kDa low-molecular-weight isoform compared to humans, who express more diverse high-molecular-weight variants.

Protein Structure and Isoforms

Fibroblast growth factor 2 (FGF2) exists in multiple isoforms arising from alternative translation initiation sites within a single mRNA transcript, with the low molecular weight (LMW) 18 kDa isoform serving as the canonical form. This LMW isoform is a 155-amino-acid polypeptide that adopts a compact β-trefoil fold, characterized by 12 antiparallel β-strands organized into three β-sheets connected by short loops, forming a stable core structure devoid of disulfide bonds due to the absence of cysteine residues.^[1]^[18]^[12] The β-trefoil architecture positions key functional regions, including a heparin-binding site primarily involving residues in the β9–β10 loop (such as Lys128 and Arg120) and receptor-binding domains on the opposite face, which facilitate interactions with extracellular matrix components and cell surface receptors.^[19] High molecular weight (HMW) isoforms of FGF2, ranging from 22 to 34 kDa, result from upstream CUG-initiated translation, introducing N-terminal extensions of approximately 24–101 amino acids to the shared C-terminal core of the LMW form.^[20] These extensions confer distinct structural features, notably nuclear localization signals (NLS); for instance, the 24 kDa isoform contains a bipartite NLS within its ~55-amino-acid extension, consisting of a basic cluster that promotes nuclear import via interaction with importin-β.^[21]^[22] Such modifications enhance the stability of HMW isoforms against proteolysis and alter their secretion dynamics, with HMW forms exhibiting reduced efficiency in conventional secretory pathways compared to the LMW isoform, often relying on non-classical export mechanisms.^[23] Post-translational modifications further diversify FGF2 structure and function. In HMW isoforms, O-glycosylation occurs at specific threonine residues within the N-terminal extensions, influencing protein folding, stability, and trafficking.^[24] Additionally, FGF2 undergoes phosphorylation by casein kinase II (CK2) at serine residues (e.g., Ser62 and Ser67 in the LMW form), which modulates its interactions with regulatory proteins and enzymatic activity.^[25]^[26] Crystal structures have elucidated these features at atomic resolution. A seminal 1994 structure (PDB: 1BAS) of bovine FGF2 reveals the monomeric β-trefoil core in isolation, highlighting the solvent-exposed heparin-binding region. Subsequent ternary complex structures, such as PDB: 1FQ9 (2000), capture human FGF2 in association with fibroblast growth factor receptor 1 (FGFR1) and heparin, demonstrating how heparin bridges two FGF2-FGFR1 units to induce symmetric dimerization and stabilize the complex.^[27] Biophysical studies confirm that FGF2 remains predominantly monomeric in aqueous solution under physiological conditions but undergoes heparin-induced dimerization, with the octasaccharide length of heparin dictating the extent of oligomerization (monomer-dimer for short chains, up to tetramers for longer ones).^[28]^[29]

Biological Functions

Cellular and Physiological Roles

Fibroblast growth factor 2 (FGF2) exerts potent mitogenic effects on multiple cell types, primarily by inducing DNA synthesis and cell cycle progression through activation of fibroblast growth factor receptors (FGFRs). In fibroblasts, FGF2 stimulates proliferation, enabling tissue remodeling and maintenance. Similarly, it promotes the proliferation of endothelial cells, supporting vascular expansion. In chondrocytes and osteoblasts, FGF2 enhances proliferative capacity, contributing to skeletal homeostasis by regulating cell numbers in cartilage and bone matrices.^[30]^[31]^[32] FGF2 plays a central role in angiogenesis by inducing endothelial cell migration, tube formation, and expression of proteases such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), which facilitate extracellular matrix degradation and vessel sprouting. These activities require heparin or heparan sulfate as a cofactor, which stabilizes FGF2-FGFR interactions and enhances signaling efficiency. Through these mechanisms, FGF2 coordinates the reorganization of endothelial cells into new vascular structures.^[33]^[17]^[34] Interactions with the extracellular matrix are critical for FGF2 function, as it binds heparan sulfate proteoglycans (HSPGs) on cell surfaces and in the matrix, thereby modulating its bioavailability and enabling the formation of concentration gradients that guide cellular responses. This binding protects FGF2 from degradation and localizes signaling to specific sites. In physiological maintenance, FGF2 supports vascular integrity by maintaining endothelial barrier function and participates in wound healing signaling pathways that promote tissue repair without overt inflammation. Additionally, FGF2 contributes to hematopoietic stem cell self-renewal by sustaining quiescence and proliferative potential in the bone marrow niche.^[35]^[34]^[17]^[36]

Developmental and Tissue Repair Functions

Fibroblast growth factor 2 (FGF2) is essential for several key processes in embryonic development, including mesoderm induction, limb bud outgrowth, and neural crest migration. In early vertebrate embryogenesis, FGF signaling, mediated by ligands such as FGF2, plays a critical role in the induction and maintenance of mesoderm, as demonstrated in Xenopus models where FGF2 induces mesodermal fates in animal cap explants.^[37] Similarly, in mouse embryos, FGF2 alters the fate of anterior epiblast cells from ectoderm to mesoderm, facilitating gastrulation movements.^[38] FGF2 also supports limb bud outgrowth by promoting proliferation and survival of mesenchymal cells,^[39] while contributing to neural crest cell migration through regulation of epithelial-mesenchymal transitions.^[40] Studies in FGF2 knockout mice reveal that these animals are viable but exhibit subtle defects in organogenesis, such as altered cardiac hypertrophy responses, highlighting FGF2's non-redundant roles in these tissues.^[41]^[42] In organogenesis, FGF2 promotes specific developmental events across multiple tissues. During eye development, FGF2 expression in the lens placode and surrounding mesenchyme supports lens fiber cell differentiation and elongation, ensuring proper lens morphogenesis.^[43] In the inner ear, FGF2 signaling influences otic vesicle patterning and sensory epithelium formation, with exogenous FGF2 application via bead implantation enhancing early morphogenetic processes.^[44] For lung development, FGF2 is expressed in early embryonic stages and regulates branching morphogenesis by stimulating epithelial proliferation and mesenchymal interactions, contributing to the formation of bronchial structures.^[45] FGF2 facilitates tissue repair by accelerating wound closure through the recruitment of fibroblasts and stimulation of collagen synthesis. In dermal wound models, FGF2 enhances fibroblast migration to the injury site and upregulates type I collagen production, leading to improved extracellular matrix deposition and faster healing.^[46]^[47] In cartilage repair contexts, such as osteoarthritis animal models, FGF2 promotes chondrocyte proliferation and cluster formation at injury sites, enhancing intrinsic repair responses and protecting against degenerative changes.^[48]^[49] Recent investigations have highlighted FGF2's involvement in hair follicle regeneration through synergy with platelet-derived growth factor AA (PDGF-AA), where the combination stimulates dermal papilla cell proliferation and anagen phase induction in preclinical models.^[50] In clinical settings, recombinant human FGF2 (rhFGF-2) has demonstrated efficacy in periodontal tissue regeneration, promoting alveolar bone and cementum formation in patients with intrabony defects when applied during surgery.^[51]^[52]

Molecular Interactions

Receptor Binding and Signaling

Fibroblast growth factor 2 (FGF2) primarily exerts its effects by binding to the family of fibroblast growth factor receptors (FGFRs), which consist of four tyrosine kinase receptors: FGFR1, FGFR2, FGFR3, and FGFR4. FGF2 exhibits high affinity for the FGFR1c isoform, with binding affinities varying across receptor subtypes due to alternative splicing in the Ig-like domain III. This interaction requires heparan sulfate proteoglycans (HSPGs) as essential co-receptors, which facilitate the formation of a complex comprising two FGF2 molecules, two FGFR molecules, and two HSPG chains. The HSPG not only stabilizes the complex but also enhances the specificity and potency of signaling by promoting receptor dimerization.^[17]^[53] The binding mechanism involves FGF2 docking to the extracellular Ig-like domains II and III (D2 and D3) of the FGFR. Domain II initiates the primary contact, while domain III confers ligand specificity through structural variations in its βC′–βE loop, influenced by splicing. Heparan sulfate bridges the two FGF2-FGFR units, forming a symmetric 2:2:2 complex that juxtaposes the intracellular kinase domains, inducing FGFR dimerization. This dimerization triggers trans-autophosphorylation of tyrosine residues in the kinase domain, activating the receptor's tyrosine kinase activity and initiating downstream signal transduction.^[54]^[53]^[55] Upon activation, FGF2-FGFR signaling engages multiple canonical intracellular pathways. The MAPK/ERK pathway is prominently activated via Ras-Raf, leading to phosphorylation of ERK1/2 and induction of transcription factors such as c-Fos and regulators of the cell cycle like Cyclin D1, which promote cell proliferation. The PI3K/AKT pathway is recruited through adapter proteins like FRS2, enhancing cell survival by inhibiting apoptosis. Additionally, PLCγ activation mobilizes intracellular calcium and PKC, supporting cell migration and differentiation. FGF2 signaling also upregulates vascular endothelial growth factor (VEGF) expression, contributing to angiogenic responses. Negative feedback is mediated by SPRY proteins, which inhibit the MAPK/ERK pathway by targeting Ras or Raf to attenuate prolonged signaling.^[56]^[17] FGF2 exists in multiple isoforms generated by alternative translation initiation, with the low-molecular-weight 18 kDa isoform primarily acting through canonical FGFR-mediated signaling, while high-molecular-weight isoforms (e.g., 21–34 kDa) possess nuclear localization signals that enable FGFR-independent translocation to the nucleus. In the nucleus, these isoforms directly regulate gene expression by interacting with chromatin or transcription factors, influencing processes like proliferation independently of receptor activation.^[57]^[58]

Protein-Protein Interactions

Fibroblast growth factor 2 (FGF2) engages in several key intracellular protein-protein interactions that modulate its phosphorylation, nuclear localization, and anti-apoptotic functions. FGF2 binds directly to the regulatory β subunit of casein kinase 2 (CK2), resulting in weak phosphorylation of FGF2 itself while stimulating CK2 autophosphorylation and altering its substrate specificity, such as toward nucleolin; this interaction facilitates FGF2's intracellular signaling and potential export mechanisms independent of the classical secretory pathway.^[59] Longer isoforms of FGF2, which predominate in the nucleus, interact with ribosomal proteins S19 (RPS19) and L6 (RPL6/TAXREB107) to support ribosome biogenesis, rRNA processing, and transcriptional regulation; for instance, FGF2 binding to RPS19 occurs in cytoplasmic extracts and aids nuclear translocation for roles in nucleolar functions, while interaction with RPL6 enhances Tax-mediated transactivation in nuclear contexts.^[60]^[61] Additional intracellular partners include apoptosis inhibitor 5 (API5), where high-molecular-weight FGF2 isoforms bind API5 to suppress caspase activation and inhibit apoptosis, particularly in growth factor-deprived conditions.^[62] Extracellularly, FGF2 interacts with heparan sulfate proteoglycans such as syndecan-1 and perlecan, which sequester it within the extracellular matrix to regulate its bioavailability and presentation to cells; syndecan-1 enhances cellular responsiveness to FGF2 by facilitating its binding and signaling, while perlecan in articular cartilage stores FGF2 in pericellular matrices to mediate localized angiogenic and repair responses.^[63]^[64]

Clinical and Research Applications

Therapeutic Uses

Recombinant human fibroblast growth factor 2 (rhFGF-2), marketed as trafermin in Japan, was approved in 2001 for the treatment of skin ulcers, including pressure sores, burn ulcers, and diabetic foot ulcers, where it promotes granulation tissue formation and accelerates wound healing through stimulation of angiogenesis and fibroblast proliferation.^[65] In 2016, trafermin was further approved in Japan under the brand name Regroth for periodontal tissue regeneration in intrabony defects, demonstrating significant radiographic bone fill (up to 3.3 mm) and probing depth reduction (up to 4.5 mm) in clinical trials compared to controls.^[66] These approvals highlight rhFGF-2's role in enhancing epithelialization and connective tissue repair without notable adverse effects in long-term follow-up.^[67] Preclinical and clinical investigations have explored rhFGF-2 for tympanic membrane perforation repair, with a phase II randomized controlled trial (NCT02307916), initiated in 2015 with estimated completion in 2016, evaluating its safety and efficacy in promoting closure of chronic non-healing perforations through local application.^[68] No results from this trial have been published as of 2025, and existing evidence from related studies shows mixed efficacy for FGF-2 in tympanic membrane repair, with a 2020 review finding no significant difference versus placebo. As of 2025, a phase II trial (NCT04960384) is evaluating FGF-2 for chronic tympanic perforations, with preliminary data suggesting potential benefits.^[69]^[70] In cardiac applications, rhFGF-2 has demonstrated cardioprotective effects post-myocardial infarction in preclinical models by promoting angiogenesis, reducing infarct size by up to 40%, and improving left ventricular function via enhanced vascularization and reduced apoptosis.^[71] Clinical translation remains limited based on historical trials, with no post-2020 early-phase trials reporting improved ejection fraction in small cohorts.^[72] In stem cell therapies, rhFGF-2 enhances induced pluripotent stem cell (iPSC) differentiation into cardiomyocytes when combined with BMP-2, increasing cardiac troponin T-positive cells by over 50% and enabling functional beating tissue for regenerative models.^[73] It is also a standard component in culture media for neural stem cells, where controlled-release formulations maintain undifferentiated proliferation and support neuronal lineage commitment at concentrations of 10-20 ng/mL, as established in seminal studies on multipotent cortical precursors.^[74] Recent advances include the development of recombinant FGF-2 secretion systems using Lactococcus lactis, a generally recognized as safe (GRAS) bacterium, which achieved a yield of 1.97 mg/L of bioactive FGF-2-G3 variant in 2025 studies, confirming its mitogenic activity on pre-adipocytic cells and potential for endotoxin-free therapeutic delivery.^[75] Preclinical work has shown that combining FGF-2 with platelet-derived growth factor (PDGF) synergistically stimulates hair follicle dermal papilla cell proliferation and inductive capacity, promoting anagen phase entry and hair shaft elongation in murine models, with applications explored in 2021 chemical reprogramming protocols.^[76] In periodontal surgery, post-2020 clinical outcomes with rhFGF-2 report sustained bone regeneration, with 4-year follow-ups indicating 61.8% of sites in the combination group (rhFGF-2 + DBBM) achieving radiographic bone fill, significantly outperforming rhFGF-2 alone (41.5%, p=0.006).^[52]

Role in Disease and Pathology

Fibroblast growth factor 2 (FGF2) plays a dual role in cancer pathology, promoting tumor progression through enhanced angiogenesis and metastasis. In various solid tumors, FGF2 overexpression stimulates vascular endothelial growth factor expression and endothelial cell proliferation, facilitating tumor neovascularization essential for growth and dissemination.^[17] Specifically, in glioblastoma, FGF2 establishes autocrine signaling loops via fibroblast growth factor receptors (FGFRs), driving glioma cell invasion and resistance to apoptosis, thereby exacerbating malignancy.^[77] Overexpression of FGF2 has been documented in a significant proportion of solid tumors, including esophageal, thyroid, and melanoma cancers, correlating with increased recurrence risk and poorer prognosis.^[78] In fibrotic and inflammatory conditions, FGF2 exhibits context-dependent effects, acting as antifibrotic in the liver while promoting fibrosis in the kidney. In non-alcoholic fatty liver disease (NAFLD), particularly in obese or overweight children, reduced circulating FGF2 levels serve as a biomarker for disease presence and progression, with post-2020 studies indicating that low FGF2 may impair hepatic repair and contribute to steatosis; exogenous FGF2 administration in models ameliorates endoplasmic reticulum stress and hepatocyte apoptosis, underscoring its protective role.^[79] Conversely, in chronic kidney disease, FGF2 drives pro-fibrotic responses by activating renal fibroblasts and tubular cells through autophagy-mediated secretion, leading to excessive extracellular matrix (ECM) deposition, collagen accumulation, and interstitial scarring.^[80] This is evidenced by elevated FGF2 in fibrotic kidneys, where FGFR2 signaling inhibition reduces fibroblast proliferation and ECM production.^[81] Neurological disorders involve dysregulated FGF2 levels and isoforms, with implications for mood and neurodegenerative pathologies. Reduced serum FGF2 concentrations are associated with heightened risk of anxiety and depression in children, potentially mediating intergenerational transmission of vulnerability through altered neurotrophic support.^[82] Salivary FGF2 levels inversely correlate with anxiety symptoms, including fear responses, suggesting its utility as a peripheral biomarker for stress-related psychiatric conditions.^[83] In Alzheimer's disease, nuclear high-molecular-weight isoforms of FGF2 provide neuroprotection by attenuating amyloid-beta-induced toxicity, oxidative stress, and neuronal death in hippocampal models, highlighting isoform-specific roles in mitigating neurodegeneration.^[84] FGF2 contributes to other pathologies by enhancing viral replication and impairing regeneration in metabolic disorders. The FGF2-FGFR axis facilitates SARS-CoV-2 entry and replication in host cells by modulating growth factor receptor signaling pathways critical for viral lifecycle support, with inhibitors reducing infectivity in vitro.^[85] In obesity-related NAFLD, diminished FGF2 expression is implicated in regeneration failure, as low levels hinder hepatocyte recovery and exacerbate lipotoxicity, linking metabolic dysfunction to progressive liver injury.^[86] As a biomarker, circulating FGF2 levels hold promise for assessing cardiovascular risk and tissue injury. Elevated serum FGF2 predicts heart failure incidence and complements natriuretic peptides in risk stratification, reflecting underlying vascular remodeling and endothelial dysfunction.^[87] Similarly, increased plasma FGF2 indicates renal tissue injury and interstitial fibrosis in glomerulonephritis, correlating with kidney injury molecule-1 for non-invasive monitoring of damage severity.^[88]

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Molecular and Clinical Significance of Fibroblast Growth Factor 2 in ...
Dec 22, 2021 · In this review, we highlight the role of FGF2 in inner ear development and hearing protection and present relevant clinical studies for tympanic membrane (TM) ...
[45]
Expression of fibroblast growth factor-2 (FGF-2) in early stages (days ...
In the mouse lung (e.g. Park et al. 1998), FGF-10 acts as a regulator of bronchial branching morphogenesis, and FGF-2 is involved in development of various ...
[46]
Fibroblast growth factor-2 bound to specific dermal ... - Nature
Dec 22, 2022 · Here we show that FGF2 binds the outer surface of dermal fibroblast (DF)-derived extracellular vesicles (EVs) and this association protects FGF2 from fast ...
[47]
Basic fibroblast growth factor induces proliferation and collagen ...
To test our hypothesis, we treated bovine luteal fibroblasts with FGF2 to measure downstream signaling, type 1 collagen production, and proliferation. We ...
[48]
Fibroblast growth factor-2 induced chondrocyte cluster formation in ...
We hypothesised that incubation of wounded articular cartilage with exogenously added FGF2 would enhance cartilage repair, replacing dead cells through ...
[49]
Fibroblast growth factor 2 is an intrinsic... : Arthritis & Rheumatism
In vitro, FGF-2 suppresses interleukin-1–driven aggrecanase activity in human cartilage explants, suggesting a chondroprotective role in vivo. We undertook this ...<|separator|>
[50]
LncRNA RP11-818O24.3 promotes hair-follicle recovery via FGF2 ...
May 19, 2024 · Kiso et al. (2015) showed that FGF2 and platelet-derived growth factor AA (PDGF-AA) can synergistically promote the proliferation of hair-follicle papilla cells ...
[51]
Recombinant human fibroblast growth factor-2 promotes surgical ...
Apr 4, 2025 · Fibroblast growth factor-2 (FGF-2) has been shown to promote periodontal tissue regeneration in clinical settings. However, reports on the effects of FGF-2 on ...
[52]
Periodontal Regenerative Therapy Using rhFGF-2 and ... - NIH
Nov 12, 2022 · Cumulative evidence from basic research indicates that FGF-2 could stimulate cells in periodontal ligament toward regeneration [3]. The regenerative ability of ...
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https://doi.org/10.1016/s1097-2765(00)00073-6
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Molecular Mechanisms of Fibroblast Growth Factor Signaling ... - NIH
Crystal structure of a ternary FGF–FGFR–heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell 6: 743–750 [DOI] [PubMed] ...Missing: II- III
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https://doi.org/10.1038/35039551
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Fibroblast growth factor signalling: from development to cancer - Nature Reviews Cancer
Summary of each segment:
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Nuclear translocation of fibroblast growth factor-2 (FGF2) is ...
We have demonstrated that nucleus-localized HMW-FGF2, but not cytoplasmic 18K-FGF2, is capable of activating the mitogenic AKT signaling and facilitating cell ...Missing: export conservation<|control11|><|separator|>
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A nuclear odyssey: fibroblast growth factor-2 (FGF-2) as a regulator ...
... FGF (FGF-1) and basic FGF (FGF-2) using isoelectric focusing [5]. Based on the tissue of origin or target cell specificity, FGF-2 was given different names like ...Fig. 1 · Fgf-2 Isoforms In The... · Nuclear Fgf-2 And...<|control11|><|separator|>
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Intracellular partners of fibroblast growth factors 1 and 2
Among the binding partners of FGF1 and FGF2 one finds protein kinases such as 90-kDa ribosomal S6 kinase 2 (RSK2) [90] and casein kinase II (CK2) [91,92].
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Analysis of the Ribosomal Protein S19 Interactome - ScienceDirect
Three proteins are known to interact with RPS19: FGF2, complement component 5 receptor 1, and a nucleolar protein called RPS19-binding protein. We have used ...Research · Results · Identification Of...
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Intracellular Association of FGF-2 with the Ribosomal Protein L6/TAXREB107
### Summary of FGF-2 Interaction with Ribosomal Protein L6/TAXREB107
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API5 confers cancer stem cell-like properties through the FGF2 ...
Jan 16, 2017 · It was suggested that API5 causes suppression of apoptosis by inhibiting caspase-3-mediated DNA fragmentation through interaction with Acinus or ...
[63]
Basal p53 expression is indispensable for mesenchymal stem cell ...
Jan 8, 2018 · Basal p53 levels are necessary to maintain MSC bi-potency, and oxygen-induced increases in p53 expression modulate cell fate and survival decisions.
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Syndecan-1 Expression Inhibits Myoblast Differentiation through a ...
These results demonstrate that syndecan-1 expression enhances cell responsiveness to bFGF and inhibits myoblast fusion and suggest that muscle terminal ...
[65]
FGF-2 is bound to perlecan in the pericellular matrix of articular ...
We hypothesised that in articular cartilage FGF-2 is stored in the extracellular matrix bound to perlecan, and that it is this pool of FGF that mediates FGF ...
[66]
Functions and transcriptional regulation of thrombospondins and ...
We found that FGF2 inhibited THBS1 and vice versa, and that THBS1 treatment decreased FGF2 expression, suggesting reciprocal inhibition. In agreement, ablation ...
[67]
FGF7 enhances the expression of ACE2 in human islet organoids ...
Apr 23, 2024 · FGF7 enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.
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FGF Family: From Drug Development to Clinical Application - PMC
After 13 years of research, trafermin was approved in 2001 in Japan for the treatment of pressure sores and skin ulcers (both burn ulcers and foot ulcers) [39] ...
[69]
Periodontal Tissue Regeneration Using Trafermin ... - ResearchGate
Aug 6, 2025 · In September 2016, trafermin (Regroth®, Kaken Pharmaceutical Co., Ltd., Tokyo) was approved for marketing as a new medication for humans to ...
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The Japanese Experience with Basic Fibroblast Growth Factor ... - NIH
Several RCTs have been conducted in Japan to examine the efficacy and safety of bFGF in treating chronic skin ulcers, diabetic ulcers, and venous ulcers. An RCT ...<|separator|>
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Fibroblast Growth Factor Regeneration of Tympanic Membrane ...
The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP).Missing: 2025 | Show results with:2025
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Basic Fibroblast Growth Factor Attenuates Injury in Myocardial ...
Aug 6, 2020 · Conclusion: The results of the present study indicated that bFGF attenuates myocardial injury by inhibiting apoptosis and promoting angiogenesis ...
[73]
Clinical Application of Novel Therapies for Coronary Angiogenesis
Apr 2, 2021 · Numerous early-phase trials of myocardial ischemia provided proof of concept that EPCs or MSCs improved vascularity in ischemic myocardial ...
[74]
The Multifunctional Contribution of FGF Signaling to Cardiac ...
The roles of FGFs in heart development range from outflow tract formation to the proliferation of cardiomyocytes and the formation of heart chambers.Missing: organogenesis | Show results with:organogenesis
[75]
FGF2 Concentration Regulates the Generation of Neurons and Glia ...
In basal medium and in low levels of FGF2, E10 stem cells exhibit a neuronal fate. Increasing the FGF2 level in the environment of multipotent cortical founder ...
[76]
Functional expression and secretion of basic fibroblast growth factor ...
Jul 24, 2025 · Conclusion. In summary, this study demonstrated that functional FGF2 can be expressed and secreted using the L. lactis expression system. We ...
[77]
Functional hair follicle regeneration: an updated review - Nature
Feb 17, 2021 · Treatment with the combination of FGF2, PDGF and 6-bromoindirubin-3′-oxime (BIO) could chemically transform human dermal fibroblasts into DPCs. SKPs can ...
[78]
Inhibition of autocrine fibroblast growth factor signaling by ... - PubMed
Autocrine fibroblast growth factor (FGF) signaling was genetically manipulated in human gliomas by an adenovirus-mediated strategy. Antisense inhibition of ...
[79]
Molecular and clinical significance of fibroblast growth factor 2 ...
In order to initiate signaling, LMW FGF2 interacts with cell surface heparan sulfate proteoglycans (HSPGs) and fibroblast growth factor receptor (FGFR) in a ...
[80]
New Biomarkers for Non-Alcoholic Fatty Liver Disease in Obese or ...
Jun 15, 2025 · Our study is pioneering in evaluating FGF-2 and TSG-6 levels in overweight or obese children diagnosed with NAFLD. A thorough literature review ...
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Ablation of FGFR2 in Fibroblasts Ameliorates Kidney Fibrosis after ...
These results suggest that FGF/FGFR2 signaling may promote the proliferation and activation of kidney fibroblasts, which contribute to the development of ...
[82]
Tubular cells produce FGF2 via autophagy after acute kidney injury ...
These results indicate that persistent autophagy after AKI induces pro-fibrotic phenotype transformation in tubular cells leading to the expression and ...
[83]
Maternal FGF2 levels associated with child anxiety and depression ...
Jan 28, 2023 · Our results point to a role for FGF2 in the intergenerational transmission of risk for, and resilience to, anxiety and depression in youth.
[84]
The Association Between Salivary FGF2 and Physiological and ...
Jul 18, 2022 · The relationship between FGF2 and anxiety appears to be causal, as peripheral FGF2 administration in adulthood or on the first day of life ...
[85]
Neuroprotective effects of LMW and HMW FGF2 against amyloid ...
The results showed that both LMW and HMW FGF2 attenuated the amyloid beta toxicity in the primary cultured hippocampal neurons as measured by WST and LDH ...Missing: nuclear | Show results with:nuclear
[86]
Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 ...
This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as a central pathway essential for SARS-CoV-2 replication.
[87]
Fibroblast growth factor 2 reduces endoplasmic reticulum stress and ...
May 9, 2023 · It was shown that fibroblast growth factor 2 ameliorated apoptosis in the NAFLD in-vitro model by reducing the expression of genes involved in the intrinsic ...
[88]
Serum fibroblast growth factor-2 levels complement vital biomarkers ...
Feb 15, 2024 · Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic ...
[89]
The significance of fibroblast growth factor-2 and kidney injury ...
Mar 10, 2022 · Serum FGF-2 and KIM-1 seem to be a non-invasive novel biomarker of interstitial renal fibrosis in glomerulonephritis patients.