Affinage

FGF5

Fibroblast growth factor 5 · UniProt P12034

Length
268 aa
Mass
29.6 kDa
Annotated
2026-06-09
95 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF5 is a secreted member of the fibroblast growth factor family that acts as a key negative regulator of the mammalian hair growth cycle, inhibiting hair elongation and driving the anagen-to-catagen transition (PMID:7923352, PMID:3211147). Genetic loss of Fgf5 in mice (null allele and the spontaneous angora mutation) and recessive loss-of-function mutations in human FGF5 (causing trichomegaly) produce abnormally long hair, while exogenous FGF5 induces follicle regression in human and mouse follicle organ culture and depilated-skin models, establishing FGF5 as a direct catagen inducer (PMID:7923352, PMID:10692103, PMID:24989505). FGF5 signals predominantly through the IIIc splice variant of FGFR1, activating the MAPK/MEK-ERK pathway to drive proliferation; gain-of-function receptor expression, dominant-negative FGFR1 IIIc, FGFR/MEK inhibitors, and FGF5-specific RNA aptamers all converge on receptor-binding-dependent mitogenesis (PMID:11876253, PMID:18362893, PMID:33536494). An alternatively spliced short form, FGF5S, which lacks exon 2, binds FGFR1 and acts as a partial antagonist: it suppresses FGF5-induced receptor tyrosine phosphorylation, blocks FGF5's catagen-promoting activity in vivo, and reverses FGF5-driven changes in dermal papilla anagen/catagen gene programs (IGF-1, versican, noggin, BMP4) (PMID:9786939, PMID:10692103, PMID:26390813). In the absence of FGF5, hair-follicle programs are de-repressed through an FGFR1→androgen/AR→Wnt/β-catenin→Shh/Gli2→c-MYC→keratin cascade, promoting secondary follicle density and fine-wool growth (PMID:32472005, PMID:38891117). Beyond the follicle, FGF5 exerts mitogenic and pro-survival autocrine/paracrine effects in glioblastoma, melanoma, and osteosarcoma via MAPK (and NFAT) signaling (PMID:18362893, PMID:31372048, PMID:29152117), regulates astroglial GFAP expression and blood-brain-barrier integrity (PMID:12878680), promotes Schwann cell migration and adhesion via N-cadherin while inhibiting ERK (PMID:32848626), and drives cardiac myocyte hypertrophy and cell-cycle re-entry (PMID:15761196).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1988 High

    Establishing that FGF5 is a bona fide secreted FGF-family protein with transforming potential defined its molecular identity and oncogenic capacity.

    Evidence cDNA cloning, sequence homology analysis, and NIH 3T3 transformation assay

    PMID:3211147

    Open questions at the time
    • Receptor and physiological function not yet defined
    • Mechanism of transformation beyond enhancer-driven overexpression not characterized
  2. 1990 Medium

    Mapping FGF5 to human chromosome 4 anchored the gene physically, enabling later genetic disease association.

    Evidence PCR-based somatic cell hybrid chromosomal assignment

    PMID:2317376

    Open questions at the time
    • No functional consequence established
    • No disease locus linkage at this stage
  3. 1994 High

    Loss-of-function genetics answered what FGF5 does physiologically, revealing it as an inhibitor of hair elongation that controls the anagen-to-catagen transition.

    Evidence Gene targeting (null allele), complementation with the spontaneous angora mutant, and in situ hybridization in hair follicles

    PMID:7923352

    Open questions at the time
    • Receptor mediating the effect not identified
    • Downstream signaling in follicle not defined
    • Source cell type of active FGF5 unclear
  4. 1998 High

    Discovery and characterization of the exon-2-skipped short form FGF5S established a built-in antagonistic regulator that competes for FGFR1 and dampens FGF5 signaling.

    Evidence cDNA cloning, RT-PCR, FGFR1 competitive binding, tyrosine phosphorylation assay, and PC12 differentiation assay; isoform-specific immunohistochemistry localized the two products to distinct skin compartments

    PMID:8611621 PMID:9786939 PMID:9856803

    Open questions at the time
    • Structural basis of partial antagonism not resolved
    • Relative in vivo abundance and regulation of splicing not quantified
  5. 1998 Medium

    Secretion polarity and promoter dissection addressed how FGF5 production and trafficking are regulated, showing basolateral vectorial secretion and differentiation-specific transcriptional repression.

    Evidence Polarized ARPE-19 conditioned-media immunoblot; FGF5 promoter/luciferase deletion constructs and EMSA in proliferating vs differentiated RPE cells

    PMID:9733582 PMID:9856785

    Open questions at the time
    • Identity of the silencer-binding nuclear proteins unknown
    • Generalizability of basolateral secretion beyond RPE untested
  6. 2000 High

    Direct protein injection confirmed the dual-mode model, showing full-length FGF5 induces catagen while FGF5S blocks that activity in vivo.

    Evidence Subcutaneous recombinant FGF5/FGF5S injection in depilated mice with histological follicle staging

    PMID:10692103

    Open questions at the time
    • Molecular signaling in follicle not measured in this assay
    • Receptor identity not directly tested here
  7. 2001 High

    Receptor-reconstitution experiments identified FGFR1 IIIc and the MEK/MAPK cascade as the route for FGF5-driven proliferation.

    Evidence Stable FGFR-1 IIIc transfection of unresponsive TAKA-1 cells, proliferation and MAPK assays, and PD98059 MEK inhibition; concurrent denervation studies linked FGF5 to Schwann cell biology

    PMID:11598998 PMID:11876253

    Open questions at the time
    • Contribution of other FGFRs not excluded
    • Co-receptor/heparan requirements not addressed
  8. 2003 High

    Knockout epistasis extended FGF5 function beyond hair to CNS, showing roles in astroglial GFAP expression and blood-brain-barrier integrity, and a receptor-binding peptide validated the FGFR-binding region as the functional determinant.

    Evidence Single/double FGF2-FGF5 mutant mice with GFAP staining, EM of endfeet, albumin extravasation, tight-junction immunoblot and astrocyte rescue; FGF5-derived decapeptide P3 competition and in vivo follicle assays

    PMID:12878680 PMID:14502567

    Open questions at the time
    • Direct cellular target of FGF5 in CNS vasculature not pinpointed
    • Redundancy with FGF2 complicates FGF5-specific attribution
  9. 2005 Medium

    Gain-of-function in myocardium revealed a direct hypertrophic and cell-cycle re-entry effect of FGF5 distinct from angiogenesis.

    Evidence Intracoronary AdvFGF-5 in hibernating swine with wall-thickening, myocyte diameter, Ki-67 and phospho-histone H3 measurements

    PMID:15761196

    Open questions at the time
    • Receptor/pathway mediating cardiac effect not identified
    • Single large-animal model
  10. 2008 High

    Autocrine/paracrine FGF5-FGFR1 IIIc signaling was established as a pro-tumorigenic axis in glioblastoma, generalizing the receptor mechanism to cancer.

    Evidence siRNA knockdown, recombinant FGF5, dominant-negative FGFR1 IIIc, FGFR inhibitors in GBM cells, plus HUVEC angiogenesis assays

    PMID:18362893

    Open questions at the time
    • Driver mutations or amplification status not addressed
    • Relative autocrine vs paracrine contribution in tumors not quantified
  11. 2016 Medium

    Subsequent cancer and vascular studies extended the MAPK/NFAT mitogenic axis to melanoma, osteosarcoma, and endothelial angiogenesis, and tied FGF5 expression to epigenetic regulation and chemoresistance.

    Evidence siRNA in aortic endothelial 3D sprouting; bidirectional manipulation in melanoma with MAPK/NFAT readouts; CRISPR KO/recombinant rescue with MAPK readout and xenograft in osteosarcoma; promoter methylation and cisplatin response in esophageal carcinoma

    PMID:27357248 PMID:29152117 PMID:31372048 PMID:31527639

    Open questions at the time
    • Receptor specificity not uniformly tested across these contexts
    • Whether NFAT activation is FGFR1-dependent unresolved
  12. 2014 High

    Human genetics and organ culture confirmed FGF5 as a direct catagen inducer in humans and linked its loss to a Mendelian phenotype.

    Evidence Whole-exome sequencing and homozygosity mapping in trichomegaly families plus human hair-follicle organ culture with recombinant FGF5

    PMID:24989505

    Open questions at the time
    • Receptor mediating human follicle regression not directly tested
    • Genotype-phenotype range across families incompletely defined
  13. 2020 Medium

    Livestock knockout and Schwann-cell studies dissected the de-repressed signaling cascades downstream of FGF5 loss and refined its receptor usage and ERK effects in nerve.

    Evidence CRISPR FGF5 KO sheep with FGFR1→AR→Wnt/β-catenin→Shh/Gli2→c-MYC→keratin pathway analysis; injured-nerve profiling, recombinant FGF5 on Schwann cells with ERK, migration, and N-cadherin assays

    PMID:26390813 PMID:32472005 PMID:32848626 PMID:38891117

    Open questions at the time
    • Direct versus indirect engagement of each cascade node not resolved
    • Context-dependent ERK inhibition vs activation by FGF5 unexplained
  14. 2022 Medium

    Overexpression studies expanded FGF5 into cytoprotective signaling, implicating CaMKII/NFκB and AKT pathways in protection from pyroptosis and oxidative stress.

    Evidence Adenoviral FGF5 overexpression in cardiomyocyte and endothelial LPS injury models with CaMKII/NFκB and AKT pathway readouts and KN93/MK2206 inhibitors

    PMID:36244113 PMID:36368152

    Open questions at the time
    • Receptor linking FGF5 to AKT/CaMKII not identified
    • Physiological relevance beyond overexpression unestablished
  15. 2024 Medium

    Dual-gene-edited sheep linked FGF5 loss to skeletal muscle satellite cell regulation through a MEK-ERK-FOSL1-MyoD1 axis.

    Evidence CRISPR MSTN Del73C + FGF5 KO sheep with MEK-ERK-FOSL1, MyoD1, and CaMKII pathway analysis and myotube phenotyping

    PMID:39365728

    Open questions at the time
    • FGF5 and MSTN effects confounded by dual editing
    • FGF5-specific contribution to the muscle phenotype not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how FGF5 switches between mitogenic, pro-survival, and ERK-inhibitory outputs across tissues, and which receptor/co-receptor configurations and FGF5S balance dictate context-specific signaling.
  • No structural model of FGF5/FGF5S-FGFR1 IIIc complex
  • Mechanistic basis for opposite ERK effects across cell types unknown
  • In vivo stoichiometry of FGF5 vs FGF5S not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
FGFR1FGFR2

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 FGF5 functions as an inhibitor of hair elongation and regulator of the anagen-to-catagen transition in the hair growth cycle. Mice homozygous for a targeted null allele (fgf5neo) or the spontaneous angora (go) mutation — shown to be a deletion in Fgf5 exon 1 — display abnormally long hair. FGF5 mRNA is expressed in the outer root sheath of hair follicles specifically during anagen VI. Gene targeting in ES cells (null allele), complementation test with spontaneous mutant (go), RNA in situ hybridization in wild-type hair follicles Cell High 7923352
1988 FGF5 encodes a secreted protein with ~40–50% amino acid homology to acidic and basic FGFs across two conserved regions (122 of 267 residues), sharing the three-exon gene structure typical of the FGF family. FGF5 transforming activity was activated by juxtaposition of a retroviral transcriptional enhancer upstream of the native promoter during transfection. cDNA cloning, sequence homology analysis, NIH 3T3 transformation assay, structural genomic analysis Molecular and cellular biology High 3211147
1998 An alternatively spliced FGF5 mRNA (FGF5S), lacking exon 2, encodes a 121–123 amino acid truncated protein. FGF5S acts as a partial agonist/antagonist of FGF5: it binds FGFR1, partially inhibits FGF5-induced FGFR1 tyrosine phosphorylation and downstream signaling, and at high concentrations partially antagonizes FGF5-induced PC12 cell differentiation, while exerting very weak neurotrophic activity alone. cDNA cloning, RT-PCR, genomic analysis, PC12 cell differentiation assays, FGFR1 tyrosine phosphorylation assay, competitive binding to FGFR1 The Journal of biological chemistry High 9786939
1996 Rat FGF5 alternative splicing generates a short-form mRNA (FGF5S) by exclusion of exon 2, encoding a 121-amino acid truncated protein whose N-terminal 117 residues are identical to those of full-length FGF5. Both FGF5 and FGF5S mRNAs are expressed in embryo and adult brain. cDNA cloning, RT-PCR, genomic exon mapping Biochimica et biophysica acta Medium 8611621
2000 FGF5 (full-length) induces catagen and inhibits hair growth during anagen when injected subcutaneously in depilated mice. FGF5S alone has no effect on hair growth but significantly inhibits the catagen-promoting activity of FGF5 when co-injected, indicating dual-mode regulation of the hair cycle by the two Fgf5 gene products. Subcutaneous injection of recombinant FGF5 and FGF5S proteins into depilated mice; histological analysis of hair follicle stage The Journal of investigative dermatology High 10692103
1998 In rat skin, FGF5 protein localizes to macrophage-like cells in the dermis (density correlated with hair cycle phase), while FGF5S protein localizes specifically to hair follicles (high in early anagen VI, decreasing in catagen), suggesting distinct compartmentalization of the two Fgf5 gene products during the hair cycle. Immunohistochemistry with isoform-specific monoclonal antibodies (E723 for FGF5 long-form; B2B6 for both forms) on rat skin sections at defined hair cycle stages The Journal of investigative dermatology Medium 9856803
1998 FGF5 is secreted vectorially from the basolateral surface of polarized RPE (ARPE-19) cells: >90% of total secreted FGF5 accumulates in basolateral media over 6 hours, as determined by immunoblot of conditioned media from adenovirus-transduced polarized monolayers. Adenovirus-mediated FGF5 gene transfer into polarized ARPE-19 monolayers; domain-selective collection and immunoblot analysis of conditioned apical vs. basolateral media Investigative ophthalmology & visual science Medium 9856785
2001 FGF5-induced mitogenesis in pancreatic ductal cells is mediated specifically through the IIIc splice variant of FGFR1 via the MAPK pathway: TAKA-1 cells that do not express FGFR1 are unresponsive to FGF5, but TAKA-1 clones stably expressing FGFR-1 IIIc show growth stimulation and enhanced MAPK activity in response to FGF5; the MEK inhibitor PD98059 blocks this effect. Stable transfection of FGFR-1 IIIc cDNA into TAKA-1 cells; cell proliferation assay; MAPK activity assay; MEK inhibitor (PD98059) treatment International journal of pancreatology High 11876253
2001 Denervated Schwann cells upregulate FGF5 mRNA and protein following axotomy; axon-Schwann cell contact suppresses FGF5 expression in regenerating sciatic nerve; forskolin also diminishes FGF5 mRNA in cultured Schwann cells, indicating that axon-Schwann cell interactions negatively regulate FGF5 expression. cDNA array screening, Northern blotting, in situ hybridization, Western blotting of axotomized rat sciatic nerve; cultured Schwann cells treated with forskolin Journal of neuroscience research Medium 11598998
2003 FGF-5 (together with FGF-2) regulates astroglial differentiation in vivo: FGF-5-/- mice show region-specific reduction in GFAP in midbrain tegmentum astrocytes. In FGF-2-/-/FGF-5-/- double mutant mice, GFAP is reduced in cortex, striatum, and midbrain, intermediate filaments in perivascular endfeet are decreased, and blood-brain barrier permeability is enhanced (albumin extravasation; reduced Occludin and ZO-1 levels). Single and double mutant mouse analysis; GFAP and S100 immunostaining; electron microscopy of perivascular endfeet; albumin extravasation assay; tight junction protein (Occludin, ZO-1) immunoblot; cortical astrocyte cultures with exogenous FGF rescue The Journal of neuroscience High 12878680
2003 A decapeptide (P3: 95-VGIGFHLQIY-104) corresponding to a receptor-binding region of FGF5 suppresses FGF5-induced proliferation of fibroblasts and FGFR-1c-expressing Ba/F3 cells in vitro, partially inhibits FGF5 binding to FGFR-1(IIIc)/Fc chimera, and reduces FGF5-induced inhibition of hair follicle growth and cell proliferation in vivo. Peptide synthesis; cell proliferation assay (BALB/3T3, NIH/3T3, FGFR-1c Ba/F3); competitive receptor-binding assay (FGFR-1(IIIc)/Fc chimera); in vivo depilated mouse model; anti-Ki67 staining of hair follicles Journal of cellular physiology Medium 14502567
2005 Adenoviral overexpression of FGF-5 in hibernating swine myocardium improves wall thickening, induces profound myocyte cellular hypertrophy, and causes a 7-fold increase in Ki-67-positive myocytes and increased phospho-histone H3-positive myocytes, demonstrating that FGF-5 directly stimulates hypertrophy and myocyte cell cycle re-entry rather than angiogenesis in cardiac muscle. Intracoronary injection of replication-deficient AdvFGF-5 in swine; echocardiographic wall-thickening measurement; histological myocyte diameter measurement; Ki-67 and phospho-histone H3 immunostaining; flow measurement Circulation research Medium 15761196
2008 FGF5 promotes GBM cell proliferation and survival via autocrine/paracrine signaling through FGFR1 IIIc: siRNA-mediated FGF5 knockdown reduces proliferation and increases apoptosis; recombinant FGF5 promotes proliferation and prevents apoptosis; dominant-negative FGFR1 IIIc or pharmacological FGFR inhibitors block these effects. FGF5 also stimulates HUVEC proliferation, migration, and tube formation (paracrine angiogenic effect). siRNA knockdown; recombinant FGF5 treatment; dominant-negative FGFR1 IIIc expression; pharmacological FGFR inhibitors; cell proliferation, apoptosis, migration assays; HUVEC tube formation assay Oncogene High 18362893
2014 Loss-of-function mutations in human FGF5 cause trichomegaly (extreme eyelash growth) inherited in an autosomal recessive pattern. Hair follicle organ culture experiments show that exogenous FGF5 protein induces regression of the human hair follicle, confirming FGF5 as a direct inducer of follicle catagen in humans. Whole exome sequencing and homozygosity mapping in trichomegaly families; hair follicle organ culture with recombinant FGF5; anagen:telogen ratio measurement Proceedings of the National Academy of Sciences of the United States of America High 24989505
2015 In cashmere goat dermal papilla cells, FGF5 overexpression upregulates IGF-1, versican, and noggin mRNA (anagen maintenance factors) and downregulates BMP4 (catagen signal); FGF5S overexpression partially reverses these effects, demonstrating FGF5S acts as an inhibitor of FGF5 function in dermal papilla cells. Adenovirus-mediated overexpression of FGF5 and FGF5S in isolated primary/secondary hair follicle dermal papilla cells; qPCR for downstream gene expression; FGFR1 expression confirmed by immunostaining Gene Medium 26390813
2019 FGF5 promotes osteosarcoma cell proliferation through activation of the MAPK signaling pathway: CRISPR/Cas9 knockout of FGF5 reduces MAPK pathway protein levels and inhibits proliferation; recombinant FGF5 addition restores MAPK activity and promotes proliferation while inhibiting apoptosis. CRISPR/Cas9 FGF5 knockout; recombinant FGF5 treatment; Western blot for MAPK pathway proteins; CCK-8 proliferation assay; xenograft nude mouse model Cancer management and research Medium 31372048
2020 FGF5 inhibits ERK1/2 MAPK activity in Schwann cells while promoting rapid Schwann cell migration and adhesion via upregulation of N-cadherin. FGF5 is strongly upregulated in Schwann cells of the distal mouse sciatic nerve following injury; FGFR1 and FGFR2 are the predominant FGF5 receptors expressed in peripheral nerve Schwann cells. Microarray and mRNA sequencing of injured sciatic nerve; RT-PCR, qPCR, Western blotting, immunostaining; recombinant FGF5 treatment of primary rat Schwann cells; ERK1/2 phosphorylation assay; migration assay; N-cadherin expression assay Frontiers in cellular neuroscience Medium 32848626
2020 In FGF5-knockout sheep, the downstream signaling cascade of FGF5 involves FGFR1 → androgen/AR → Wnt/β-catenin → Shh/Gli2 → c-MYC → keratins, and crosstalk between androgen and Wnt/β-catenin signaling contributes to increased fine-wool and active hair-follicle density when FGF5 is absent. CRISPR/Cas9 FGF5 KO in Dorper sheep; qPCR for FGF5 mRNA; H&E and immunohistochemistry; Western blot for pathway components; pathway inhibitor/activator experiments Cell death & disease Medium 32472005
2021 RNA aptamers selected against human FGF5 bind FGF5 with high affinity and specificity (Kd = 0.7 nM for F5f1; Kd = 0.118 nM for truncated F5f1_56) and inhibit FGF5-induced cell proliferation without inhibiting FGF2-induced proliferation, establishing that FGF5 receptor-binding activity drives its mitogenic effect. SELEX (aptamer selection); surface plasmon resonance binding assay; FGF5-induced cell proliferation inhibition assay; cross-reactivity testing with FGF1, FGF2, FGF4, FGF6, FGFR1 Scientific reports Medium 33536494
1998 FGF5 gene expression in differentiated RPE cells is controlled by a proximal promoter/enhancer active between sequences -314 and +48 (not cell-context dependent), and a silencer element (-1256/-883) active only in differentiated RPE cells. Specific nuclear proteins from differentiated (but not proliferating) RPE cells bind to two small distal promoter regions (-1195/-1173 and -984/-967), suggesting differentiation-specific transcriptional repression of FGF5. Transient transfection of FGF5 promoter/luciferase deletion constructs in proliferating vs. differentiated RPE cells; gel mobility shift assays with differentiated/proliferating nuclear extracts Experimental eye research Medium 9733582
2022 FGF5 overexpression in cardiomyocytes reduces LPS-induced pyroptosis and oxidative stress by inhibiting CaMKII/NFκB signaling: FGF5 overexpression decreases p-CaMKII, p-NFκB, NLRP3, caspase-1, IL-1β and IL-18 levels; the CaMKII inhibitor KN93 recapitulates FGF5's protective effects. Adenovirus-mediated FGF5 overexpression in vivo (mouse LPS model) and in vitro (cardiomyocytes); echocardiography; Western blot for CaMKII, NFκB, NLRP3, caspase-1, IL-1β, IL-18; KN93 pharmacological inhibition Biochemical and biophysical research communications Medium 36368152
2022 FGF5 overexpression protects endothelial cells from LPS-induced pyroptosis via activation of AKT signaling: FGF5 overexpression activates AKT, and the AKT inhibitor MK2206 abolishes FGF5's protective effect in HUVECs exposed to LPS. FGF5 overexpression in mouse ALI model and HUVECs; pyroptosis assay; Western blot for AKT; pharmacological inhibition with MK2206 Biochemical and biophysical research communications Medium 36244113
2019 FGF5 promoter methylation in esophageal squamous cell carcinoma represses FGF5 expression. Cisplatin treatment induces FGF5 expression in unmethylated cell lines but not methylated ones; exogenous FGF5 overexpression in a methylated cell line confers resistance to cisplatin, indicating FGF5 expression modulates chemotherapy response. Bisulfite pyrosequencing for methylation; qPCR/Western blot for FGF5 expression; cisplatin treatment of cell lines with varying methylation status; FGF5 overexpression in methylated cell line; clonogenic survival assay Scientific reports Medium 31527639
2016 FGF2 and FGF5 intrinsic to human aortic endothelial cells (HAECs) promote angiogenesis: siRNA knockdown of FGF2 and FGF5 significantly attenuates VEGF-A-stimulated vascular sprouting from HAECs (but less so from HUVECs), demonstrating an autocrine/paracrine angiogenic role for FGF5 in aortic endothelial cells. 3D microfluidic angiogenesis system; siRNA knockdown of FGF2 and FGF5 in HAECs and HUVECs; quantification of vascular sprouting; qPCR for FGF2/FGF5 expression Scientific reports Medium 27357248
2000 FGF5 misexpression in the developing chick limb (via RCAS retroviral vector) severely inhibits mature myocyte formation (reduced MyoD and myosin heavy chain expression) and simultaneously stimulates proliferation and expansion of tenascin-expressing connective tissue fibroblasts and perichondrial cells, as measured by BrdU incorporation. RCAS retroviral overexpression of human FGF5 in chick embryo hindlimb; immunostaining for MyoD, myosin heavy chain, tenascin; BrdU pulse labeling for proliferation; histological analysis Developmental dynamics Medium 11066093
2001 Adeno-associated virus-mediated FGF-5 delivery to the subretinal space of P23H and S334ter transgenic rats rescues photoreceptors from cell death. Post-injection, FGF-5 protein localizes to inner and outer segments of photoreceptors, and FGFR1 and FGFR2 are upregulated in these regions, suggesting rescue is mediated by receptor tyrosine kinase signaling in photoreceptors. Subretinal AAV injection; morphological and ERG functional analysis; immunocytochemistry for FGF-5, FGFR1, FGFR2 localization Molecular therapy Medium 11319911
2017 FGF5 overexpression in human melanoma cells increases clonogenicity and invasion (but not short-term growth) in vitro, and enhances tumor growth, proliferation index, and angiogenesis in vivo. These effects are associated with increased signaling along the MAPK and NFAT axes but no effect on STAT3 signaling. Silencing FGF5 in high-FGF5 melanoma cells has opposite effects. FGF5 overexpression and siRNA silencing in melanoma cell lines; clonogenicity and invasion assays; xenograft in vivo model; Ki-67 and apoptosis assays; signaling pathway Western blots; tissue microarray immunohistochemistry Oncotarget Medium 29152117
2024 FGF5 editing in sheep decreases cortisol concentration in skin, activates antioxidant enzyme GSH-Px, and modulates Wnt signaling pathway components (Rspondins as agonists, Notum as antagonist) in hair follicle regeneration, promoting secondary hair follicle development and fine wool growth. CRISPR/Cas9 FGF5 editing in Dorper sheep; cortisol measurement; GSH-Px activity assay; qPCR and Western blot for Wnt pathway components; histological analysis of hair follicle density Cells Medium 38891117
2024 FGF5 knockout (combined with MSTN Del73C mutation) in sheep activates FOSL1 via the MEK-ERK-FOSL1 axis; activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by suppressing MyoD1 expression, resulting in smaller myotubes; activated ERK1/2 also inhibits secondary myotube fusion via Ca2+-dependent CaMKII activation. CRISPR/Cas9 dual-gene edited sheep (MSTN Del73C + FGF5 KO); Western blot for MEK-ERK-FOSL1 pathway; MyoD1 expression analysis; myotube morphology; CaMKII pathway analysis; F0 and F1 phenotyping eLife Medium 39365728
2025 FGF5 overexpression suppresses ferroptosis in renal tubular epithelial cells subjected to ischemia-reperfusion-like injury by activating mitophagy, reducing oxidative stress and inflammatory responses. FGF5 overexpression in NRK-52E and HK-2 cells; cell viability assay; oxidative stress markers; inflammatory cytokine assay; mitophagy assessment; ferroptosis markers Journal of molecular histology Low 40913740
1990 The FGF5 oncogene was mapped to human chromosome 4 by PCR-based somatic cell hybrid analysis. PCR amplification of FGF5 sequences from somatic cell hybrid DNAs containing defined human chromosomes BioTechniques Medium 2317376

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations. Cell 483 7923352
1988 The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors. Molecular and cellular biology 427 3211147
1991 mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation. Development (Cambridge, England) 179 1794311
2015 MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma. Journal of hepatology 161 25998163
2014 FGF5 is a crucial regulator of hair length in humans. Proceedings of the National Academy of Sciences of the United States of America 137 24989505
2015 Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. Scientific reports 134 26354037
2003 Functions of fibroblast growth factor (FGF)-2 and FGF-5 in astroglial differentiation and blood-brain barrier permeability: evidence from mouse mutants. The Journal of neuroscience : the official journal of the Society for Neuroscience 126 12878680
1998 Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5. Investigative ophthalmology & visual science 111 9856785
2008 FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities. Oncogene 86 18362893
2005 Adenoviral gene transfer of FGF-5 to hibernating myocardium improves function and stimulates myocytes to hypertrophy and reenter the cell cycle. Circulation research 80 15761196
2007 Mutations within the FGF5 gene are associated with hair length in cats. Animal genetics 79 17433015
2000 Dual-mode regulation of hair growth cycle by two Fgf-5 gene products. The Journal of investigative dermatology 76 10692103
1992 Coexpression of FGF-5 and bFGF by the retinal pigment epithelium in vitro. Experimental eye research 76 1478282
2006 The long and the short of it: evidence that FGF5 is a major determinant of canine 'hair'-itability. Animal genetics 69 16879338
2011 Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans. Journal of hypertension 68 20852445
2001 Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18. Molecular therapy : the journal of the American Society of Gene Therapy 67 11319911
2016 Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers. PloS one 66 27755602
1998 Localization of rat FGF-5 protein in skin macrophage-like cells and FGF-5S protein in hair follicle: possible involvement of two Fgf-5 gene products in hair growth cycle regulation. The Journal of investigative dermatology 56 9856803
2016 Intrinsic FGF2 and FGF5 promotes angiogenesis of human aortic endothelial cells in 3D microfluidic angiogenesis system. Scientific reports 54 27357248
2013 Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs. Animal genetics 50 23384345
2017 CRISPR/Cas9-mediated loss of FGF5 function increases wool staple length in sheep. The FEBS journal 46 28631368
2020 Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep. Cell death & disease 45 32472005
2015 Fibroblast growth factor 5-short (FGF5s) inhibits the activity of FGF5 in primary and secondary hair follicle dermal papilla cells of cashmere goats. Gene 42 26390813
2014 Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys. Genetics, selection, evolution : GSE 39 25927731
2019 Downregulation of miR-145-5p elevates retinal ganglion cell survival to delay diabetic retinopathy progress by targeting FGF5. Bioscience, biotechnology, and biochemistry 34 31272285
1994 Distribution of FGF-5 in the rhesus macaque retina. Investigative ophthalmology & visual science 34 8045713
2019 Base pair editing in goat: nonsense codon introgression into FGF5 results in longer hair. The FEBS journal 32 31276295
2019 FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway. Cancer management and research 32 31372048
2018 MicroRNA-567 inhibits cell proliferation, migration and invasion by targeting FGF5 in osteosarcoma. EXCLI journal 31 29743851
2000 FGF5 stimulates expansion of connective tissue fibroblasts and inhibits skeletal muscle development in the limb. Developmental dynamics : an official publication of the American Association of Anatomists 31 11066093
1998 An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity. The Journal of biological chemistry 31 9786939
2021 Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice. Frontiers in pharmacology 30 34305588
2020 Hsa_circ_0016760 exacerbates the malignant development of non‑small cell lung cancer by sponging miR‑145‑5p/FGF5. Oncology reports 28 33416186
2017 FGF5 is expressed in melanoma and enhances malignancy in vitro and in vivo. Oncotarget 28 29152117
2017 RAPID COMMUNICATION: Generation of FGF5 knockout sheep via the CRISPR/Cas9 system. Journal of animal science 26 28727005
1996 The rat FGF-5 mRNA variant generated by alternative splicing encodes a novel truncated form of FGF-5. Biochimica et biophysica acta 26 8611621
2017 Promotion of anagen, increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process. Clinical, cosmetic and investigational dermatology 25 28280377
2003 Decapeptide with fibroblast growth factor (FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF-5. Journal of cellular physiology 25 14502567
2020 FGF5 Regulates Schwann Cell Migration and Adhesion. Frontiers in cellular neuroscience 24 32848626
2013 Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans. BMC evolutionary biology 24 23394579
1990 Chromosome assignment by polymerase chain reaction techniques: assignment of the oncogene FGF-5 to human chromosome 4. BioTechniques 23 2317376
2021 Specific inhibition of FGF5-induced cell proliferation by RNA aptamers. Scientific reports 21 33536494
1997 Expression of FGF5 in choroidal neovascular membranes associated with ARMD. Current eye research 20 9134330
2021 Five SNPs Within the FGF5 Gene Significantly Affect Both Wool Traits and Growth Performance in Fine-Wool Sheep (Ovis aries). Frontiers in genetics 18 34659356
2018 Expression of Fibroblast Growth Factor 5 (FGF5) and Its Influence on Survival of Breast Cancer Patients. Medical science monitor : international medical journal of experimental and clinical research 18 29804124
2011 Retrotransposon-mediated Fgf5(go-Utr) mutant mice with long pelage hair. Experimental animals 18 21512271
2024 A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia. eLife 17 39365728
2022 FGF5 protects heart from sepsis injury by attenuating cardiomyocyte pyroptosis through inhibiting CaMKII/NFκB signaling. Biochemical and biophysical research communications 17 36368152
2016 Visualization of the Epiblast and Visceral Endodermal Cells Using Fgf5-P2A-Venus BAC Transgenic Mice and Epiblast Stem Cells. PloS one 17 27409080
2001 Expression of the IIIc variant of FGF receptor-1 confers mitogenic responsiveness to heparin and FGF-5 in TAKA-1 pancreatic ductal cells. International journal of pancreatology : official journal of the International Association of Pancreatology 17 11876253
2019 FGF5 methylation is a sensitivity marker of esophageal squamous cell carcinoma to definitive chemoradiotherapy. Scientific reports 16 31527639
2015 A 1-bp deletion in Fgf5 causes male-dominant long hair in the Syrian hamster. Mammalian genome : official journal of the International Mammalian Genome Society 16 26481120
1997 Transient expression of FGF-5 mRNA in the rat cerebellar cortex during post-natal development. Brain research. Molecular brain research 16 9221924
2022 Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population. Molecular genetics and genomics : MGG 14 35380267
2021 SP1-induced lncRNA TUG1 regulates proliferation and apoptosis in islet cells of type 2 diabetes mellitus via the miR-188-3p/FGF5 axis. European review for medical and pharmacological sciences 14 33660806
2017 Molecular characterization of the llama FGF5 gene and identification of putative loss of function mutations. Animal genetics 14 29024003
2001 Axon-Schwann cell interactions regulate the expression of fibroblast growth factor-5 (FGF-5). Journal of neuroscience research 14 11598998
2014 Molecular cloning, characterization, and expression of sheep FGF5 gene. Gene 13 25445274
2012 Cloning and expression analysis of Fgf5, 6 and 7 during early chick development. Gene expression patterns : GEP 11 22634565
2019 Eclipta prostrata promotes the induction of anagen, sustains the anagen phase through regulation of FGF-7 and FGF-5. Pharmaceutical biology 10 30757935
2021 FGF5 and EPAS1 gene polymorphisms are associated with high-altitude adaptation in Nepalese goat breeds. Animal science journal = Nihon chikusan Gakkaiho 9 34585489
2022 The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis. Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists 8 35880306
2018 Evidence of post-transcriptional readthrough regulation in FGF5 gene of alpaca. Gene 8 29307854
2023 Circ_0001715 Functions as a miR-1249-3p Sponge to Accelerate the Progression of Non-small Cell Lung Cancer via Upregulating the Level of FGF5. Biochemical genetics 7 36808266
2022 Circ_0041732 regulates tumor properties of triple-negative breast cancer cells by the miR-149-5p/FGF5 pathway. The International journal of biological markers 7 35341378
2008 [Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits]. Yi chuan = Hereditas 7 18779133
2001 Expression of the IIIc Variant of FGF Receptor-1 Confers Mitogenic Responsiveness to Heparin and FGF-5 in TAKA-1 Pancreatic Ductal Cells. International journal of gastrointestinal cancer 7 12754391
2024 Increasing GSH-Px Activity and Activating Wnt Pathway Promote Fine Wool Growth in FGF5-Edited Sheep. Cells 6 38891117
2023 Reproduction and viscera organ characteristics of MSTN and FGF5 dual-gene knockout sheep. Frontiers in veterinary science 6 37065235
2021 FGF5 missense mutation is associated with dromedary hair length variation. Animal genetics 6 34432312
2015 Alpaca fiber growth is mediated by microRNA let-7b via down-regulation of target gene FGF5. Genetics and molecular research : GMR 6 26535691
2023 Potential roles of FGF5 as a candidate therapeutic target in prostate cancer. American journal of clinical and experimental urology 5 38148937
2022 A 90-Day Safety Study of Meat from MSTN and FGF5 Double-Knockout Sheep in Wistar Rats. Life (Basel, Switzerland) 5 35207492
2022 FGF5 alleviated acute lung injury via AKT signal pathway in endothelial cells. Biochemical and biophysical research communications 5 36244113
2015 Cloning, molecular characterization, and expression pattern of FGF5 in Cashmere goat (Capra hircus). Genetics and molecular research : GMR 5 26400346
2009 [Effects of FGF5 gene on fibre traits on Inner Mongolian cashmere goats]. Yi chuan = Hereditas 5 19273426
1998 Differentiation of retinal pigment epithelial cells in vitro uncovers silencer activity in the FGF-5 gene promoter. Experimental eye research 5 9733582
2025 Multi-Omics Characterization of Genome-Wide Abnormal DNA Methylation Reveals FGF5 as a Diagnosis of Nasopharyngeal Carcinoma Recurrence After Radiotherapy. Biomolecules 4 40001587
2024 Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits. Genes 4 38674344
2024 Metabolic differences in MSTN and FGF5 dual-gene edited sheep muscle cells during myogenesis. BMC genomics 4 38926663
2023 Global Long Noncoding RNA Expression Profiling of MSTN and FGF5 Double-Knockout Sheep Reveals the Key Gatekeepers of Skeletal Muscle Development. DNA and cell biology 4 36917699
2022 Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations. International journal of molecular sciences 4 36233155
2023 Fibroblast growth factor 5 (FGF5) and its missense mutant FGF5-H174 underlying trichomegaly: a molecular dynamics simulation investigation. Journal of biomolecular structure & dynamics 3 36905676
2023 A rare FGF5 candidate variant (rs112475347) for predisposition to nonsquamous, nonsmall-cell lung cancer. International journal of cancer 3 36916144
2023 FGF5. Differentiation; research in biological diversity 3 37957094
2022 Tracing the Origin of the RSPO2 Long-Hair Allele and Epistatic Interaction between FGF5 and RSPO2 in Sapsaree Dog. Genes 3 35052442
2022 The rs1458038 variant near FGF5 is associated with poor response to calcium channel blockers among Filipinos. Medicine 3 35119014
2012 [Interaction of mutant genes Fgf5(go-Y), we, and wal changes the duration of hair growth cycles in mice]. Ontogenez 3 22567929
1999 Technology evaluation: gene therapy (FGF-5), Vical. Current opinion in molecular therapeutics 3 11715949
2011 [Cloning, expression analysis and RNA interference of FGF5 gene in sheep]. Yi chuan = Hereditas 1 21951799
2026 FGF5 Allelic Heterogeneity in Long-Haired Belgian Shepherd Dogs. Animal genetics 0 41773981
2026 Discovery of Four New FGF5 Variants Causing Long Hair in the Dog. Animals : an open access journal from MDPI 0 41828909
2026 Integrative Genomic Analyses Identify COL21A1 and ENPEP-FGF5 Regulatory Pathways for Blood Pressure Variation in East Asians. bioRxiv : the preprint server for biology 0 42239286
2025 Genetic Variant of the Canine FGF5 Gene for the Hair Length Trait in the Akita: Utility for Hair Coat Variations and Welfare in Conservation Breeding. Genes 0 40869975
2025 FGF5 alleviates ferroptosis in renal tubular epithelial cells by inducing mitophagy under in vitro ischemia-reperfusion-like injury. Journal of molecular histology 0 40913740

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