Affinage

FGF7

Fibroblast growth factor 7 · UniProt P21781

Length
194 aa
Mass
22.5 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF7 (KGF) is a secreted, heparin-binding growth factor that drives epithelial proliferation, survival, differentiation, and migration by signaling through a single high-affinity receptor, FGFR2 IIIb (KGFR), engaged with exquisite specificity through residues in its β4/β5 loop and contacts with the alternatively spliced D3 region of the receptor (PMID:1846048, PMID:14527678, PMID:30809251). This receptor selectivity restricts FGF7's action to epithelia, and its activity additionally depends on a glycosaminoglycan co-receptor: in skin, dermatan sulfate rather than heparan sulfate is the principal physiological cofactor enabling FGF7-dependent receptor binding and signaling (PMID:12215437, PMID:7528211). Receptor engagement is read out through several context-dependent intracellular cascades — Ras-MAPK/ERK1/2 for proliferation and motility (PMID:9660480, PMID:15672868, PMID:19266047), PI3K-Akt(-S6K) for epithelial survival and differentiation (PMID:11446769, PMID:12732722, PMID:19266047), and JNK for maintenance of alveolar type II cell identity (PMID:17872496) — with these arms feeding distinct transcriptional effectors (SREBP-1 for lipogenesis, C/EBP-β for integrin α5, β-catenin in osteocytes) (PMID:16162944, PMID:17596295, PMID:30287900). At the tissue level, FGF7-FGFR2 IIIb signaling is required for epidermal morphogenesis and wound reepithelialization (PMID:7973639), directs surface-ectoderm cell fate including apical ectodermal ridge induction and epidermal-versus-follicle choice (PMID:10373311, PMID:19474150), and orchestrates fibrosis and wound contraction through double-paracrine loops in which FGF7 stimulates keratinocytes to secrete OSM or TGF-β1 that then activate fibroblasts (PMID:23096718, PMID:30894415). Beyond epithelia, FGF7 acts as a presynaptic organizer of inhibitory synapses, being transported by KIF5/gephyrin to inhibitory postsynaptic sites (PMID:25431136), and as a stromal mediator of regeneration that drives muscle satellite-cell proliferation (PMID:38751367). In cancer, autocrine and stromal FGF7-FGFR2 loops promote invasion, EMT, and therapy resistance via MMP/uPA induction, PI3K/Akt/mTOR-THBS1, and HIF-1α stabilization (PMID:10389758, PMID:28339036, PMID:35428876, PMID:38491511).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Established that KGF/FGF7 acts through its own dedicated high-affinity tyrosine kinase receptor distinct from the bFGF receptor, defining the ligand-receptor axis that all later mechanism rests on.

    Evidence Expression cDNA cloning and ligand-binding competition with transformation assay in NIH/3T3 fibroblasts

    PMID:1846048

    Open questions at the time
    • Did not define which epithelial cell types depend on this receptor in vivo
    • Structural basis of specificity not yet resolved
  2. 1994 High

    Demonstrated that KGFR signaling in basal keratinocytes is physiologically required for epidermal morphogenesis and wound reepithelialization, moving FGF7 from a biochemical activity to an in vivo tissue function.

    Evidence Dominant-negative KGFR transgene in mouse keratinocytes with skin histology and wound-healing assays

    PMID:7973639

    Open questions at the time
    • Dominant-negative blocks all FGFR2 IIIb ligands, not FGF7 specifically
    • Downstream signaling not dissected
  3. 1994 High

    Showed that cell-surface heparan sulfate modulates rather than universally promotes FGF7 binding, raising the question of which glycosaminoglycan is the true physiological co-receptor.

    Evidence Radioligand binding with chlorate/heparinase treatment in KGFR-expressing cell lines

    PMID:7528211

    Open questions at the time
    • Identity of the physiological co-receptor not resolved here
    • Low-affinity binding site left unidentified
  4. 2002 High

    Identified dermatan sulfate as the principal skin glycosaminoglycan cofactor enabling FGF7-dependent receptor binding and signaling, resolving the co-receptor question for wounds.

    Evidence GAG-panel reconstitution with radiolabeled FGF7 binding, MAPK phosphorylation, and proliferation in BaF/KGFR cells and keratinocytes

    PMID:12215437

    Open questions at the time
    • Whether dermatan sulfate serves as co-receptor in non-skin tissues unknown
    • Structural geometry of the FGF7-dermatan-receptor complex not defined
  5. 2003 High

    Provided the structural basis for FGF7's exclusive FGFR2 IIIb specificity by mapping ligand residues that contact the exon-IIIb region, explaining receptor selectivity at atomic resolution.

    Evidence Structure-based mutagenesis of FGF7 with receptor binding-affinity and activity assays

    PMID:14527678

    Open questions at the time
    • No experimental co-crystal structure reported in this entry
    • Contribution of GAG to specificity addressed only later
  6. 2001 High

    Dissected the downstream signaling logic, showing FGF7 activates ERK-MAPK, PI3K-Akt/S6K, and JNK arms that are deployed differentially for proliferation, survival, and differentiation in distinct epithelia.

    Evidence Pharmacological and genetic pathway dissection (wortmannin, rapamycin, PD98059, dominant-negative Akt, JNKK2) with proliferation/survival/differentiation readouts across corneal, pancreatic, alveolar, and breast cells

    PMID:11446769 PMID:12732722 PMID:15672868 PMID:17872496 PMID:19266047 PMID:9660480

    Open questions at the time
    • What determines pathway selection in a given cell type remains unclear
    • Receptor-proximal adapter usage (Shc/Grb2/Sos) appears context-dependent and incompletely resolved
  7. 2005 High

    Connected FGF7 signaling arms to specific transcription-factor effectors, showing PI3K/JNK→SREBP-1 drives lipogenic gene expression and ERK→C/EBP-β drives integrin α5, defining transcriptional outputs.

    Evidence Promoter reporter mutagenesis, dominant-negative SREBP-1/C/EBP-β, and siRNA in pulmonary and keratinocyte models

    PMID:16162944 PMID:20

    Open questions at the time
    • Effector usage may be cell-type restricted
    • Integration of multiple transcription factors not modeled
  8. 1999 High

    Established FGF7's role in surface-ectoderm fate decisions, including apical ectodermal ridge induction and cell-fate reprogramming, distinguishing it functionally from other FGF family members.

    Evidence Chick bead implantation/ectoderm explants with Fgf8 in situ and lens-specific KGF transgenic mice

    PMID:10373311 PMID:10525187

    Open questions at the time
    • Molecular mediators of fate change not fully defined
    • Relationship to FGFR2 IIIb signaling arms not dissected here
  9. 2007 High

    Revealed signaling kinetics as a determinant of morphogenetic outcome — transient FGF7-driven ERK promotes growth without branching and dominates over branching-inducing TGFα signals.

    Evidence Ex vivo mammary explant culture with ERK time-course and morphological/molecular readouts

    PMID:17448457

    Open questions at the time
    • Mechanism setting ERK duration not identified
    • Generalizability to other branched epithelia untested
  10. 2014 High

    Identified FGF7 as a presynaptic organizer of inhibitory synapses delivered to postsynaptic sites by motor/adaptor machinery, extending FGF7 function beyond epithelia into neurons.

    Evidence Live imaging and KIF5/gephyrin knockdown in hippocampal neurons with synapse-targeting assays

    PMID:25431136

    Open questions at the time
    • Receptor mediating the synaptic-organizing activity not defined here
    • In vivo significance for inhibitory circuits untested
  11. 2012 Medium

    Defined double-paracrine epithelial-mesenchymal loops (KGF→keratinocyte→OSM/TGF-β1→fibroblast) as the mechanism for FGF7-driven fibrosis and wound contraction.

    Evidence Conditioned-medium experiments, neutralizing antibodies, STAT3/Smad signaling readouts, and collagen-lattice contraction with in vivo wound models

    PMID:23096718 PMID:30894415

    Open questions at the time
    • Single-lab mechanisms
    • Relative contributions of OSM versus TGF-β1 loops in different contexts unclear
  12. 2015 High

    Placed FGF7 downstream of GLP-1 receptor signaling as a required mediator of intestinal mucosal growth, linking it into a systemic hormone-growth axis via genetic epistasis.

    Evidence Fgf7-knockout mice with exendin-4 treatment and overlapping gene-expression analysis in Apc(Min/+) models

    PMID:25738454

    Open questions at the time
    • Cellular source and target of Fgf7 in this axis not fully defined
    • Receptor-level mechanism not dissected
  13. 2022 Medium

    Established autocrine and stromal FGF7-FGFR2 loops as drivers of cancer invasion, EMT, hormone-receptor crosstalk, and targeted-therapy resistance across multiple tumor types.

    Evidence FGFR2/THBS1 knockdown, HIF-1α ubiquitination assays, ER-PR co-IP, SOX9/WNT3A manipulation, and in vivo neutralizing antibodies in gastric, ovarian, breast, and cholangiocarcinoma models

    PMID:10389758 PMID:28339036 PMID:35428876 PMID:35726195 PMID:38491511

    Open questions at the time
    • Each cancer mechanism shown in a single lab
    • Whether the same pathway operates across tumor types not cross-validated
  14. 2024 Medium

    Extended FGF7-FGFR2 signaling to regenerative niche communication, with fibro-adipogenic progenitor-derived FGF7 driving muscle satellite-cell proliferation and regeneration.

    Evidence scRNA-seq/CellChat interaction analysis, FGFR2 knockdown, EdU assays, and injury/aging mouse models

    PMID:38751367

    Open questions at the time
    • Intracellular pathway in satellite cells not fully mapped
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ligand-receptor pair selects among ERK, Akt, and JNK arms to produce opposing outcomes (proliferation vs. differentiation vs. survival) in different cell types remains the central unresolved mechanistic question.
  • No unifying model linking co-receptor identity, signaling kinetics, and effector selection
  • Structural co-crystal of the FGF7-FGFR2 IIIb-GAG ternary complex not reported in the corpus
  • Receptor for neuronal/synaptic FGF7 activity unconfirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3
Partners
FGFR2GPHNKIF5

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 KGF (FGF7) signals through a specific high-affinity tyrosine kinase receptor (KGFR/FGFR2 IIIb) that is distinct from the basic FGF receptor; expression cloning in NIH/3T3 fibroblasts demonstrated acquisition of specific high-affinity KGF binding sites and transformation via an autocrine loop. Expression cDNA cloning, ligand binding competition assays, focus formation/transformation assay Science High 1846048
1994 KGF receptor signaling in basal keratinocytes is required for normal epidermal morphogenesis and reepithelialization of wounds; dominant-negative KGFR transgene in mice caused epidermal atrophy, hair follicle abnormalities, dermal hyperthickening, and substantially delayed wound reepithelialization with reduced keratinocyte proliferation at wound edges. Dominant-negative transgene expression in mouse basal keratinocytes, skin histology, wound healing assay Science High 7973639
1994 Cell-associated heparan sulfates differentially modulate KGF binding to KGFR: heparin inhibits KGF binding to KGFR whereas it enhances aFGF binding to the same receptor; removal of cell-surface heparan sulfates (chlorate treatment or heparinase) enhances KGF high-affinity binding ~2-fold. KGF also interacts with an unidentified low-affinity binding site unaffected by heparan sulfate removal. Radioligand binding assays, sodium chlorate treatment to block proteoglycan sulfation, heparinase/heparitinase digestion, competition binding in L6E9 cells expressing KGFR and Balb/MK cells The Journal of biological chemistry High 7528211
1996 The KGF/FGF7 promoter is directly regulated by androgens; androgen treatment (R1881) upregulates KGF promoter activity 6–11 fold in LNCaP cells, with the androgen-responsive element located in the region -900 to -1200 upstream of the transcription start site. Promoter deletion constructs, transient transfection luciferase assays in LNCaP cells, transcription start site mapping Biochemical and biophysical research communications Medium 8607856
1997 KGF prevents H2O2-induced increases in airway epithelial cell permeability through a PKC-dependent mechanism that stabilizes the F-actin cytoskeleton; calphostin C (PKC inhibitor) abolished both KGF-mediated basal barrier enhancement and its protective effect. Fluorescein isothiocyanate-albumin permeability assay across Transwell monolayers, pharmacological inhibitor (calphostin C), F-actin immunostaining The American journal of physiology Medium 9142942
1997 KGF increases DNA repair capacity in irradiated pulmonary epithelial cells through DNA polymerases-α, -δ, and -ε (but not polymerase-β); aphidicolin and butylphenyl dGTP blocked the KGF-mediated reduction in radiation-induced DNA strand breaks, whereas dideoxythymidine triphosphate did not. 137Cs gamma irradiation, alkaline DNA unwinding/ethidium bromide fluorescence assay, selective DNA polymerase inhibitors The American journal of physiology Medium 9227520
1998 KGF activates Ras-MAPK (p42/p44 ERK) pathway in human corneal epithelial cells; KGF did not activate the Jak-STAT cascade (STAT1, STAT3, Jak1). Unlike HGF, KGF did not induce phosphorylation of adapter protein Shc or receptor coimmunoprecipitation with Grb2/Sos1. Immunoprecipitation, Western blot for MAPK activation, gel retardation/EMSA, kinase inhibitors (PD098059, calphostin C, genistein) Investigative ophthalmology & visual science Medium 9660480
1999 FGF7 and FGF10 directly induce the apical ectodermal ridge (AER) in chick embryos, activating Fgf8 expression in cultured flank ectoderm without mesoderm; FGF7 and FGF10 but not FGF1, -2, or -4 induced ectopic AER in dorsal median ectoderm. Ectopic bead implantation in chick embryos, ectoderm explant culture without mesoderm, in situ hybridization for Fgf8 Developmental biology High 10373311
1999 FGF7 triggers invasive potential and anchorage-independent growth in human prostatic epithelial cells via an autocrine loop; FGF7-transfected PNT1A cells overexpressed MMP-1 and uPA, and invasion was specifically blocked by FGF7-neutralizing antibody. Stable cDNA transfection, extracellular matrix invasion assay, soft agar growth assay, neutralizing antibody, Western blot for MMP-1 and uPA International journal of cancer Medium 10389758
1999 Lens-specific overexpression of KGF (FGF7) in transgenic mice caused hyperproliferation of embryonic corneal epithelial cells and their differentiation into functional lacrimal gland-like tissues, demonstrating that KGF receptor stimulation in surface ectoderm is sufficient to alter cell fate toward lacrimal gland. Transgenic mouse overexpression (lens-specific promoter), histology, immunohistochemistry Mechanisms of development Medium 10525187
2001 KGF activates PI3K and its downstream target p70 S6 kinase in corneal epithelial cells; PI3K inhibitor wortmannin, PKC inhibitor calphostin C, and rapamycin all blocked KGF-induced p70 S6K activation and KGF-stimulated corneal epithelial wound healing in an organ culture model. MEK1 inhibitor PD98059 had no effect on p70 S6K activation. PI3K activity assay, p70 S6K phosphorylation/activity assay, pharmacological inhibitors, corneal organ culture wound healing model Experimental eye research Medium 11446769
2002 Dermatan sulfate (chondroitin sulfate B), the predominant glycosaminoglycan in skin, is the principal cofactor for FGF7 activity in wounds; dermatan sulfate enabled FGF7-dependent KGFR (FGFR2 IIIb) binding, MAPK phosphorylation, and proliferation of BaF/KGFR cells and normal keratinocytes. Heparan sulfate and chondroitin sulfate A/C did not support FGF7 activity. Cell proliferation assay (BaF/KGFR lymphoid cells and keratinocytes), radiolabeled FGF7 binding assay, MAPK phosphorylation Western blot, comparative GAG panel The Journal of biological chemistry High 12215437
2003 KGF-induced activation of the Akt (PI3K) signaling axis mediates protection of lung alveolar epithelial cells from hyperoxia-induced cell death; dominant-negative Akt blocked KGF-mediated epithelial cell survival in vitro and in vivo, and the protective effect was selective for epithelial (not endothelial) cells consistent with selective KGFR expression. Tetracycline-inducible transgenic lung-specific KGF expression, dominant-negative Akt transfection, in vitro and in vivo hyperoxia cell death assays Proceedings of the National Academy of Sciences High 12732722
2003 FGF7-induced breast cancer cell motility requires Grb2 and ERK1/2 (but not Akt) downstream of KGFR tyrosine kinase activation; Grb2 knockdown and ERK1/2 inhibition (PD98059) suppressed KGF-induced motility, while wortmannin (PI3K/Akt inhibitor) did not. Time-lapse video microscopy, culture wound assay, Grb2 antisense knockdown, pharmacological inhibitors (genistein, PD98059, wortmannin) Clinical & experimental metastasis Medium 15672868
2003 Structure-based mutagenesis identified specific FGF7 residues (β4/β5 loop, Asp63, Leu142, Arg65) that are required for interaction with the unique exon IIIb region of FGFR2IIIb; mutations at these residues reduced receptor binding affinity and biological activity, explaining FGF7's exclusive specificity for FGFR2IIIb. Computational structural modeling of FGFR2IIIb/FGF7 complex, site-directed mutagenesis, receptor binding affinity measurements, biological activity assays FEBS letters High 14527678
2005 KGF-induced proliferation in pancreatic ductal cells is mediated through the MEK-ERK1/2 pathway; KGF-induced ductal cell differentiation (PDX1 and Glut2 expression) is mediated through PI3K/AKT. Inactivation of MEK/ERK by pharmacological inhibitor or antisense morpholino-oligonucleotides abolished KGF-induced duct cell proliferation both in vitro and in vivo. BrdU incorporation (in vitro and in vivo), pharmacological MEK inhibitor, antisense morpholino-oligonucleotides against MEK1, immunolocalization of PDX1/Glut2, PI3K inhibition PloS one Medium 19266047
2005 KGF induces lipogenesis in pulmonary epithelial cells (H292) via PI3K and JNK signaling pathways converging on SREBP-1 transcription factor, which in turn drives expression of FAS and SCD-1; dominant-negative SREBP-1 adenovirus blocked KGF effects on FAS and SCD-1; mutation of the SREBP-1 binding site in SCD-1 promoter abolished KGF induction. Pharmacological inhibitors (LY294002, SP600125, PD98059), luciferase promoter constructs, adenovirus-mediated dominant-negative SREBP-1 overexpression, Western blot for Akt/S6K/JNK/ERK activation Journal of lipid research High 16162944
2007 FGF7-induced MAPK(ERK1,2) activation in mammary epithelium is transient (15 min) and promotes growth without branching, whereas TGFα induces sustained ERK activation (1 h) sufficient for branching morphogenesis; FGF7 suppresses TGFα-induced MMP-3 and fibronectin expression, dominating over TGFα when both are applied simultaneously. Ex vivo mammary explant culture, ERK1/2 activity time-course assays, morphological analysis of branching, inhibitor experiments, keratin-6 immunostaining Developmental biology High 17448457
2007 KGF signaling in thymic epithelial cells (TECs) activates p53 and NF-κB pathways, induces BMP2, BMP4, Wnt5b, and Wnt10b expression, and canonical BMP pathway signaling is required for KGF effects on TEC expansion and T-cell development. In vivo KGF administration to mice, flow cytometry of thymic subsets, gene expression analysis, pathway inhibition studies Blood Medium 17213286
2007 KGF maintains the alveolar type II (AT2) cell phenotype through JNK (c-Jun N-terminal kinase) activation; JNK inhibition (but not ERK1/2 or p38 inhibition) abolished KGF-mediated maintenance of AT2 phenotype markers (p180). Overexpression of JNKK2 (upstream JNK kinase) increased c-Jun activation and promoted retention of AT2 markers. Primary rat AEC culture, selective MAPK inhibitors, JNKK2 overexpression, AT2/AT1 phenotype markers (p180, AQP5, VIIIB2), microarray American journal of respiratory cell and molecular biology Medium 17872496
2007 KGF increases integrin α5 expression in keratinocytes through ERK1/2-dependent phosphorylation of the C/EBP-β transcription factor; dominant-negative C/EBP-β inhibited α5 promoter activity and siRNA knockdown of C/EBP-β diminished integrin α5 expression. Promoter reporter assays, ERK1/2 inhibition, dominant-negative C/EBP-β expression, C/EBP-β siRNA knockdown, Western blot, 3D epidermis tissue analogue American journal of physiology. Cell physiology Medium 17596295
2009 KGF (FGF7)/FGFR2IIIb signaling inhibits hair follicle induction and promotes interfollicular epidermal fate; KGF blocked follicle formation in embryonic skin organ culture in a time- and dose-dependent manner, and downstream molecular markers showed epidermal differentiation was promoted at the expense of hair follicle fate. Embryonic skin organ culture, growth factor treatment, microarray profiling, molecular marker analysis, KGFR/EGFR expression mapping Development Medium 19474150
2012 Increased KGF expression in fibroblasts promotes cutaneous fibrosis through a double paracrine mechanism: KGF stimulates keratinocytes to produce and secrete oncostatin M (OSM), which in turn activates fibroblasts; OSM-mediated STAT3 phosphorylation upregulates urokinase plasminogen activator, increasing collagen type I-α1 expression and fibroblast migration. KGF stimulation of keratinocytes, conditioned medium experiments, ELISA for OSM, Western blot for STAT3 phosphorylation, collagen expression, migration assays The Journal of investigative dermatology Medium 23096718
2014 FGF7 induces autophagy in human keratinocytes through a PI3K-AKT-MTOR-independent mechanism, stimulating autophagosome formation; upon prolonged stimulation FGF7 also accelerates autophagosome turnover. Autophagy was required for FGF7-mediated early keratinocyte differentiation, as BECN1 and ATG5 depletion counteracted FGF7-induced KRT1 upregulation. Biochemical autophagy markers (LC3, p62), quantitative fluorescence microscopy, autophagosome-lysosome fusion block, siRNA depletion of BECN1 and ATG5, PI3K/AKT/mTOR inhibitors Autophagy Medium 24577098
2014 FGF7 is selectively targeted to inhibitory postsynaptic sites in hippocampal neurons where it acts as a presynaptic organizer for inhibitory synapse differentiation; inhibitory synaptic targeting of FGF7 requires the motor protein KIF5 and adaptor gephyrin; time-lapse imaging showed FGF7 co-moves with gephyrin along microtubules. Selective synaptic targeting analysis, KIF5 and gephyrin knockdown, time-lapse live imaging, co-transport assays, SAP102/PSD95 knockdown effects on FGF7 localization Journal of cell science High 25431136
2015 GLP-1 receptor signaling promotes intestinal mucosal growth through a mechanism requiring Fgf7; exendin-4 failed to increase intestinal growth in Fgf7-knockout mice, and exendin-4 increased Fgf7 expression in colonic polyps; exendin-4 and Fgf7 regulated an overlapping set of intestinal growth genes. Fgf7 knockout mice, exendin-4 treatment, Apc(Min/+) mouse model, gene expression analysis Cell metabolism High 25738454
2017 FGF7/FGFR2 signaling promotes invasion and migration of human gastric cancer cells through upregulation of thrombospondin-1 (THBS1) via the PI3K/Akt/mTOR pathway; FGFR2 knockdown partially suppressed FGF7-induced invasion/migration, and THBS1 knockdown similarly reduced these effects. FGFR2 knockdown, THBS1 knockdown, in vitro invasion/migration assays, PI3K/Akt/mTOR pathway inhibition, Western blot International journal of oncology Medium 28339036
2018 FGF7 promotes osteocyte cell process formation and gap junctional communication through connexin43 (Cx43) via FGF7-induced cytoplasmic accumulation and nuclear translocation of β-catenin; β-catenin signaling mediated FGF7's upregulation of Cx43 expression in MLO-Y4 osteocyte cells. qRT-PCR, Western blot, immunofluorescence for Cx43 and β-catenin localization, nuclear fractionation, cell process morphology analysis in MLO-Y4 cells Scientific reports Medium 30287900
2019 KGF-1 accelerates wound contraction through a double-paracrine mechanism: KGF-1 stimulates keratinocytes to produce TGF-β1, which then activates fibroblasts; this leads to increased Col-I, p-Smad2, p-Smad3, and α-SMA expression. TGF-β1-neutralizing antibody attenuated the KGF-1-induced contractile capacity of fibroblast-populated collagen lattices. Keratinocyte-fibroblast co-culture, ELISA for TGF-β1, fibroblast-populated collagen lattice contraction assay, TGF-β1 neutralizing antibody, Western blot for Smad pathway components, diabetic rat wound model The Journal of biological chemistry Medium 30894415
2019 FGF7 structural subfamily analysis: members of the FGF7 subfamily (FGF3, FGF7, FGF10, FGF22) achieve restricted specificity for FGFR1b/FGFR2b by engaging specific contacts with two alternatively spliced loop regions in the immunoglobulin-like domain 3 (D3) of these receptors; weak basal receptor-binding affinity further constrains specificity; heparin sulfate co-receptor affinity differences among the four members contribute to their disparate biological activities. Structural analysis review (compilation of crystal structures and mutagenesis data from the field) Frontiers in genetics Medium 30809251
2021 FGF7 promotes osteoblast dendrite elongation and functional gap junction formation by increasing E11 expression; E11 directly interacted with Cx43 in primary osteoblasts; MAPK and PI3K-AKT pathways were involved in FGF7-mediated E11 upregulation and cell process formation. Co-immunoprecipitation (E11-Cx43 interaction), Western blot, immunofluorescence, pathway inhibitors (MAPK, PI3K-AKT), osteoblast morphology analysis International journal of biological sciences Medium 34671204
2022 FGF7/FGFR2 signaling abolishes progesterone receptor (PR)-mediated modulation of estrogen receptor (ER) activity in luminal breast cancer; FGF7/FGFR2 signaling regulated ER and PR expression and activity, increased ER-PR complex formation, reversed P4-triggered ER-dependent gene deregulation, and required JunB as a prerequisite for abrogating P4-induced growth inhibition. 3D cell growth assays, hormone receptor expression and activity assays (ER/PR), ER-PR co-immunoprecipitation, gene expression analysis, JunB functional requirement assays Molecular oncology Medium 35726195
2022 SOX9, activated by WNT3A via TCF7, enhances FGF7 transcription and expression in cholangiocarcinoma; secreted FGF7 activates FGFR2 phosphorylation in an autocrine pathway promoting CCA proliferation and pemigatinib resistance. mRNA sequencing, in vitro/in vivo validation, WNT3A stimulation, SOX9 overexpression/knockdown, FGFR2 phosphorylation assay, autocrine secretion measurement Oncogene Medium 35428876
2024 Fibro-adipogenic progenitors (FAPs) interact with muscle satellite cells (MuSCs) via FGF7-FGFR2 signaling to promote MuSC proliferation; FGFR2 knockdown in MuSCs abolished the pro-proliferative effects of exogenous FGF7; FGF7 administration increased satellite cell proliferation and enhanced muscle regeneration in injury and aging models. Single-cell RNA sequencing, CellChat cell-cell communication analysis, FGFR2 knockdown, EdU proliferation assays, cardiotoxin injury model, d-galactose aging model, in vivo muscle function assays Journal of cachexia, sarcopenia and muscle Medium 38751367
2024 Cancer-associated fibroblast-derived FGF7 promotes ovarian cancer progression by inhibiting ubiquitination and degradation of HIF-1α via FGFR2 interaction, activating the FGF7/HIF-1α/EMT axis; neutralizing antibodies against FGF7 substantially reduced tumor growth in vivo. In vitro invasion/migration/proliferation assays, single-cell transcriptomic analysis, HIF-1α ubiquitination assay, FGFR2 interaction studies, in vivo neutralizing antibody treatment Journal of translational medicine Medium 38491511

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science (New York, N.Y.) 504 7973639
1991 Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop. Science (New York, N.Y.) 442 1846048
2005 Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration. Blood 178 16304055
2007 Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells. Blood 172 17213286
2007 The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium. Developmental biology 156 17448457
1999 Expression of HGF, KGF, EGF and receptor messenger RNAs following corneal epithelial wounding. Experimental eye research 152 10192796
2015 GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7. Cell metabolism 119 25738454
2003 Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia. Proceedings of the National Academy of Sciences of the United States of America 118 12732722
2017 FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. International journal of oncology 111 28339036
2022 Scarless wound healing: Current insights from the perspectives of TGF-β, KGF-1, and KGF-2. Cytokine & growth factor reviews 88 35690568
2002 Dermatan sulfate binds and potentiates activity of keratinocyte growth factor (FGF-7). The Journal of biological chemistry 87 12215437
2009 KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin. Development (Cambridge, England) 82 19474150
1998 KGF increases SP-A and SP-D mRNA levels and secretion in cultured rat alveolar type II cells. American journal of respiratory cell and molecular biology 81 9476903
2005 KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells. Journal of lipid research 75 16162944
2004 Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model. Gene therapy 73 15470477
1999 FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. The Journal of urology 73 10411093
2012 Increased KGF expression promotes fibroblast activation in a double paracrine manner resulting in cutaneous fibrosis. The Journal of investigative dermatology 71 23096718
1997 KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells. The American journal of physiology 70 9227520
1997 KGF prevents hydrogen peroxide-induced increases in airway epithelial cell permeability. The American journal of physiology 69 9142942
1994 Differential effect of cell-associated heparan sulfates on the binding of keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF receptor. The Journal of biological chemistry 69 7528211
1999 FGF7 and FGF10 directly induce the apical ectodermal ridge in chick embryos. Developmental biology 67 10373311
2001 HGF- and KGF-induced activation of PI-3K/p70 s6 kinase pathway in corneal epithelial cells: its relevance in wound healing. Experimental eye research 60 11446769
2001 Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF. American journal of physiology. Cell physiology 60 11546667
2019 Structural Biology of the FGF7 Subfamily. Frontiers in genetics 59 30809251
2002 Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. Gene therapy 52 12140734
2018 miR-381-3p restrains cervical cancer progression by downregulating FGF7. Journal of cellular biochemistry 50 30161290
2015 Azilsartan reduced TNF-α and IL-1β levels, increased IL-10 levels and upregulated VEGF, FGF, KGF, and TGF-α in an oral mucositis model. PloS one 47 25689279
1999 Keratinocyte growth factor (KGF) promotes keratinocyte cell attachment and migration on collagen and fibronectin. Cell adhesion and communication 47 10626905
1998 Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak-STAT pathways. Investigative ophthalmology & visual science 46 9660480
2005 Fibroblast growth factor (FGF)-1, FGF2, FGF7 and FGF receptors are uniformly expressed in trophoblast giant cells during restricted trophoblast invasion in cows. Placenta 45 16129484
2003 Glutamine and KGF each regulate extracellular thiol/disulfide redox and enhance proliferation in Caco-2 cells. American journal of physiology. Regulatory, integrative and comparative physiology 45 12947032
2009 Mechanisms of KGF mediated signaling in pancreatic duct cell proliferation and differentiation. PloS one 44 19266047
2002 Trefoil peptide expression and goblet cell number in rat intestine: effects of KGF and fasting-refeeding. American journal of physiology. Regulatory, integrative and comparative physiology 43 12388439
1999 FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells. International journal of cancer 43 10389758
1999 Ectopic gland induction by lens-specific expression of keratinocyte growth factor (FGF-7) in transgenic mice. Mechanisms of development 42 10525187
1998 Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation. Molecular reproduction and development 42 9547510
2022 Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway. Oncogene 40 35428876
2019 KGF-1 accelerates wound contraction through the TGF-β1/Smad signaling pathway in a double-paracrine manner. The Journal of biological chemistry 40 30894415
2019 Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis. Cancer management and research 40 31308741
2000 Expression and action of keratinocyte growth factor (KGF) in normal ovarian surface epithelium and ovarian cancer. Molecular and cellular endocrinology 40 11000522
2000 KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT. American journal of physiology. Lung cellular and molecular physiology 39 10781430
2024 Single-cell RNA-seq reveals novel interaction between muscle satellite cells and fibro-adipogenic progenitors mediated with FGF7 signalling. Journal of cachexia, sarcopenia and muscle 36 38751367
2020 KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats. BMJ open diabetes research & care 36 32434772
2007 Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling. American journal of respiratory cell and molecular biology 36 17872496
2003 Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 14656992
1996 Androgen regulation of the rat keratinocyte growth factor (KGF/FGF7) promoter. Biochemical and biophysical research communications 36 8607856
2018 Neuroprotective effects of overexpressed microRNA-200a on activation of glaucoma-related retinal glial cells and apoptosis of ganglion cells via downregulating FGF7-mediated MAPK signaling pathway. Cellular signalling 35 30439502
1997 Differential expression of the keratinocyte growth factor (KGF) and KGF receptor genes in human vascular smooth muscle cells and arteries. Journal of cellular physiology 34 9369951
2020 MicroRNA-107 Ameliorates Damage in a Cell Model of Alzheimer's Disease by Mediating the FGF7/FGFR2/PI3K/Akt Pathway. Journal of molecular neuroscience : MN 33 32472396
2014 FGF7/KGF regulates autophagy in keratinocytes: A novel dual role in the induction of both assembly and turnover of autophagosomes. Autophagy 33 24577098
2012 Cholesteatoma-associated fibroblasts modulate epithelial growth and differentiation through KGF/FGF7 secretion. Histochemistry and cell biology 33 22481617
2016 Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects. Journal of bone and mineral metabolism 32 27766421
2011 Plantaricin A synthesized by Lactobacillus plantarum induces in vitro proliferation and migration of human keratinocytes and increases the expression of TGF-β1, FGF7, VEGF-A and IL-8 genes. Peptides 32 21782870
2012 KGF-2 targets alveolar epithelia and capillary endothelia to reduce high altitude pulmonary oedema in rats. Journal of cellular and molecular medicine 29 22568566
2008 KGF-1 for wound healing in animal models. Methods in molecular biology (Clifton, N.J.) 29 18370216
2007 AKT and MAPK signaling in KGF-treated and UVB-exposed human epidermal cells. Journal of cellular physiology 29 17458890
2006 Elevated expression of FGF7 protein is common in human gastric diseases. Biochemical and biophysical research communications 29 17049492
2001 Differential expression analysis by gene array of cell cycle modulators in human corneal epithelial cells stimulated with epidermal growth factor (EGF), hepatocyte growth factor (HGF), or keratinocyte growth factor (KGF). Current eye research 27 11821989
2021 LncRNA BCRT1 facilitates osteosarcoma progression via regulating miR-1303/FGF7 axis. Aging 26 34102610
2019 Improved stability of KGF by conjugation with gold nanoparticles for diabetic wound therapy. Nanomedicine (London, England) 26 31791171
2024 Microneedle Patch for Transdermal Sequential Delivery of KGF-2 and aFGF to Enhance Burn Wound Therapy. Small (Weinheim an der Bergstrasse, Germany) 25 38623988
2021 Cell-subpopulation alteration and FGF7 activation regulate the function of tendon stem/progenitor cells in 3D microenvironment revealed by single-cell analysis. Biomaterials 25 34810035
2014 Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7. Journal of cell science 25 25431136
2006 Expression of fibroblast growth factor 1 (FGF1) and FGF7 in mature follicles during the periovulatory period after GnRH in the cow. The Journal of reproduction and development 25 16415522
1996 Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC. European journal of cancer. Part B, Oral oncology 25 8736168
1999 KGF and FGF-10 stimulate liquid secretion in human fetal lung. Pediatric research 23 10541313
2022 Protection of Human Lens Epithelial Cells from Oxidative Stress Damage and Cell Apoptosis by KGF-2 through the Akt/Nrf2/HO-1 Pathway. Oxidative medicine and cellular longevity 22 35222803
2020 MiR-199a-3p inhibits the proliferation, migration, and invasion of endothelial cells and retinal pericytes of diabetic retinopathy rats through regulating FGF7 via EGFR/PI3K/AKT pathway. Journal of receptor and signal transduction research 22 32586178
2002 Keratinocyte Growth Factor (KGF) in hematology and oncology. Current pharmaceutical design 22 12069377
2024 Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter. Journal of translational medicine 21 38491511
2013 FGF7 and cell density are required for final differentiation of pancreatic amylase-positive cells from human ES cells. Cell and tissue research 21 23996199
1997 Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF. The American journal of physiology 21 9316491
2019 Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway. Journal of molecular and cellular cardiology 20 30858037
2018 KGF inhibits hypoxia-induced intestinal epithelial cell apoptosis by upregulating AKT/ERK pathway-dependent E-cadherin expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 30021369
2018 FGF-7 Dictates Osteocyte Cell Processes Through Beta-Catenin Transduction. Scientific reports 20 30287900
2004 KGF-induced motility of breast cancer cells is dependent on Grb2 and Erk1,2. Clinical & experimental metastasis 20 15672868
2022 FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer. Molecular oncology 19 35726195
2022 circCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis. Journal of oncology 19 35783154
2021 FGF7-induced E11 facilitates cell-cell communication through connexin43. International journal of biological sciences 19 34671204
2019 Comparative Analysis of KGF-2 and bFGF in Prevention of Excessive Wound Healing and Scar Formation in a Corneal Alkali Burn Model. Cornea 19 31490279
2018 TGF beta inhibits HGF, FGF7, and FGF10 expression in normal and IPF lung fibroblasts. Physiological reports 19 30155985
2005 Comparative genomics on FGF7, FGF10, FGF22 orthologs, and identification of fgf25. International journal of molecular medicine 19 16142419
1998 Induction of KGF, basic FGF, and TGFalpha mRNA expression during healing of experimental TM perforations. Acta oto-laryngologica 19 9840508
2023 BFNB Enhances Hair Growth in C57BL/6 Mice through the Induction of EGF and FGF7 Factors and the PI3K-AKT-β-Catenin Pathway. International journal of molecular sciences 18 37569486
2014 In vivo over-expression of KGF mimic human middle ear cholesteatoma. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 18 25138153
2007 KGF promotes integrin alpha5 expression through CCAAT/enhancer-binding protein-beta. American journal of physiology. Cell physiology 18 17596295
2006 Keratinocyte growth factor (KGF) induces tamoxifen (Tam) resistance in human breast cancer MCF-7 cells. Anticancer research 18 16827106
2005 FGF7-like gene is associated with pericentric inversion of chromosome 9, and FGF7 is involved in the development of ovarian cancer. International journal of oncology 18 15809711
2003 Keratinocyte growth factor (KGF) decreases ICAM-1 and VCAM-1 cell expression on bronchial epithelial cells. Clinical and experimental immunology 18 12653837
2000 Pattern of expression of the KGF receptor and its ligands KGF and FGF-10 during postnatal mouse mammary gland development. Molecular reproduction and development 18 10911393
2012 Potential dual role of KGF/KGFR as a target option in novel therapeutic strategies for the treatment of cancers and mucosal damages. Expert opinion on therapeutic targets 17 22443411
2008 Keratinocyte growth factor receptor (KGF-R) in cholesteatoma tissue. Acta oto-laryngologica 17 18368565
1998 Mammogenic hormones differentially modulate keratinocyte growth factor (KGF)-induced proliferation and KGF receptor expression in cultured mouse mammary gland epithelium. Endocrinology 17 9564867
2020 Hyperphosphatemia with low FGF7 and normal FGF23 and sFRP4 levels in the circulation characterizes pediatric hypophosphatasia. Bone 16 32112990
2013 Protection against hyperoxia-induced lung fibrosis by KGF-induced MSCs mobilization in neonatal rats. Pediatric transplantation 16 23919829
2003 Structure-based mutational analyses in FGF7 identify new residues involved in specific interaction with FGFR2IIIb. FEBS letters 16 14527678
2003 Antisense KGFR oligonucleotide inhibition of KGF-induced motility in breast cancer cells. Anticancer research 16 14981945
2021 Exosome-transmitted circ-CARD6 facilitates posterior capsule opacification development by miR-31/FGF7 axis. Experimental eye research 15 33844960
2021 FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas. Molecular oncology 15 34850536
2004 Improved production of recombinant fibroblast growth factor 7 (FGF7/KGF) from bacteria in high magnesium chloride. Protein expression and purification 15 14711521

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