Affinage

FGF7

Fibroblast growth factor 7 · UniProt P21781

Length
194 aa
Mass
22.5 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF7 (also known as KGF) is a mesenchyme-derived paracrine growth factor that signals exclusively through the epithelial-specific receptor FGFR2 IIIb to drive epithelial proliferation, differentiation, survival, and morphogenesis across diverse tissues including skin, lung, prostate, intestine, and thymus (PMID:2475908, PMID:1846048, PMID:7973639). Receptor specificity is conferred by FGF7's β4/β5 loop and residues Asp63, Leu142, and Arg65 engaging the alternatively spliced D3 domain of FGFR2b, with dermatan sulfate serving as the principal glycosaminoglycan co-receptor in skin (PMID:14527678, PMID:12215437). Downstream, FGF7 activates PI3K/Akt, ERK1/2, JNK, and p38 MAPK in a context-dependent manner — ERK drives proliferation and motility, PI3K/Akt mediates survival and differentiation, JNK controls epithelial phenotype maintenance and lipogenesis, and p38 governs progenitor cell differentiation — while also inducing autophagy-dependent keratinocyte differentiation and double paracrine loops (via TGF-β1, OSM, or IL-1α) that coordinate epithelial–mesenchymal crosstalk in wound healing and tissue remodeling (PMID:12732722, PMID:16162944, PMID:17872496, PMID:16554439, PMID:24577098, PMID:30894415, PMID:23096718). Beyond epithelial tissues, FGF7 functions in hippocampal neurons where it is transported to inhibitory postsynaptic sites via KIF5/gephyrin-mediated microtubule transport to organize inhibitory presynaptic differentiation (PMID:25431136).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1989 High

    The identity of a stromal-derived epithelial mitogen was unknown; cloning FGF7/KGF from fibroblast-conditioned medium established it as a novel FGF family member with expression restricted to stromal cells of epithelial tissues, defining the mesenchymal-to-epithelial paracrine paradigm.

    Evidence cDNA cloning and expression analysis from human fibroblast-conditioned medium

    PMID:2475908

    Open questions at the time
    • No receptor identified
    • Downstream signaling unknown
    • In vivo function not established
  2. 1991 High

    The receptor mediating KGF's epithelial specificity was unknown; identification of FGFR2 IIIb as the KGF receptor explained why KGF acts exclusively on epithelial cells that express this splice variant.

    Evidence Expression cDNA library screen with autocrine transformation assay in NIH/3T3 cells, receptor binding competition

    PMID:1846048

    Open questions at the time
    • Structural basis for receptor selectivity unknown
    • Co-receptor requirements not defined
    • In vivo requirement not tested
  3. 1994 High

    Whether KGF receptor signaling was required for epithelial homeostasis in vivo was untested; dominant-negative KGFR in transgenic mice demonstrated that this pathway is essential for normal epidermal morphogenesis, hair follicle development, and wound reepithelialization.

    Evidence Dominant-negative KGFR transgenic mouse, histology and proliferation assays at wound edges

    PMID:7973639

    Open questions at the time
    • Downstream signaling pathways not dissected
    • Relative contribution of FGF7 versus other FGFR2b ligands (FGF10, FGF22) not resolved
  4. 1996 Medium

    The role of FGF7 in organ morphogenesis beyond skin was unclear; work in prostate organ culture showed FGF7 mediates androgen-driven ductal branching morphogenesis via mesenchyme-epithelium paracrine signaling, and its promoter contains androgen-responsive elements.

    Evidence Prostate organ culture with anti-KGF neutralizing antibody and soluble KGFR; promoter-reporter assays with androgen stimulation in LNCaP cells

    PMID:8607856 PMID:8946242

    Open questions at the time
    • Androgen-responsive element identity not fully mapped
    • Whether other FGFs compensate in vivo unknown
  5. 1997 Medium

    The cytoprotective mechanisms downstream of KGF were undefined; studies in airway epithelial cells revealed PKC-dependent barrier protection and F-actin stabilization, and enhanced DNA repair capacity through replicative DNA polymerases α, δ, and ε.

    Evidence Transwell permeability with PKC inhibitors; alkaline unwinding DNA damage assay with selective polymerase inhibitors in pulmonary epithelial cells

    PMID:9142942 PMID:9227520

    Open questions at the time
    • Direct PKC isoform not identified
    • Connection between DNA repair induction and receptor signaling cascades not mapped
  6. 2002 High

    The glycosaminoglycan co-receptor for FGF7 was assumed to be heparan sulfate by analogy with other FGFs; dermatan sulfate was identified as the principal co-receptor in skin, uniquely enabling FGFR2 IIIb binding, MAPK activation, and keratinocyte proliferation.

    Evidence Reconstituted receptor binding, MAPK phosphorylation, and proliferation assays with fractionated GAGs in BaF/KGFR cells

    PMID:12215437

    Open questions at the time
    • Structural basis of dermatan sulfate–FGF7 interaction not resolved
    • Whether other tissues use different co-receptor GAGs unknown
  7. 2003 High

    The structural determinants of FGF7's exclusive FGFR2b specificity were unknown; structure-based mutagenesis identified the β4/β5 loop and residues Asp63, Leu142, and Arg65 as critical for receptor binding and biological activity.

    Evidence Site-directed mutagenesis guided by structural modeling, receptor binding and activity assays

    PMID:14527678

    Open questions at the time
    • No co-crystal structure of FGF7–FGFR2b complex at that time
    • Contribution of each residue to affinity versus specificity not fully deconvolved
  8. 2003 High

    How KGF protects epithelial cells from oxidative death was mechanistically undefined; inducible KGF expression in mouse lung demonstrated PI3K/Akt activation selectively in epithelial cells, and dominant-negative Akt blocked KGF-mediated protection from hyperoxia.

    Evidence Tetracycline-inducible KGF transgenic mice, dominant-negative Akt, in vivo and in vitro cell death assays

    PMID:12732722

    Open questions at the time
    • Downstream Akt substrates mediating survival not identified
    • Whether Akt is required for all KGF cytoprotective effects unknown
  9. 2005 Medium

    Context-dependent divergence of MAPK branches downstream of KGF was unresolved; JNK and PI3K (but not ERK) were shown to drive KGF-induced lipogenesis via SREBP-1 in pulmonary epithelial cells, while ERK drove proliferation and motility in other contexts.

    Evidence Pharmacological inhibitors, dominant-negative/active SREBP-1 constructs, promoter mutagenesis in H292 cells; Grb2 knockdown and ERK inhibition in breast cancer motility assays

    PMID:15672868 PMID:16162944

    Open questions at the time
    • How the same receptor activates different MAPK branches in different cell types not explained
    • In vivo relevance of KGF-driven lipogenesis not tested
  10. 2007 Medium

    How KGF maintains epithelial cell identity versus driving differentiation through specific MAPK branches was unclear; JNK/c-Jun was shown to maintain alveolar type II cell phenotype, p38 was shown to drive prostatic and limbal epithelial differentiation, and ERK-C/EBPβ controlled integrin α5 expression in keratinocytes.

    Evidence Selective MAPK inhibitors with JNKK2 overexpression in primary rat AECs; p38 inhibitor and siRNA in prostate TAP cells and limbal explants; DN-C/EBPβ and siRNA in keratinocytes

    PMID:16554439 PMID:17596295 PMID:17872496 PMID:19920075

    Open questions at the time
    • How pathway selection is determined at the receptor level unknown
    • Cross-talk between JNK, p38, and ERK branches not dissected
  11. 2000 Medium

    Upstream regulators and paracrine feedback circuits controlling FGF7 expression were incompletely defined; IL-1α from prostatic epithelial cells was identified as the paracrine inducer of FGF7 in stromal cells, establishing a double paracrine loop.

    Evidence Conditioned medium with anti-IL-1α neutralizing antibodies and IL-1Ra in prostatic cell co-cultures

    PMID:10880394

    Open questions at the time
    • Whether IL-1α–FGF7 loop operates in non-prostatic tissues not tested
    • Transcription factors mediating IL-1α induction of FGF7 not identified
  12. 2012 Medium

    The mechanism by which KGF coordinates epithelial-mesenchymal crosstalk beyond direct epithelial stimulation was unclear; KGF was shown to induce keratinocyte secretion of oncostatin M, which activates fibroblasts via STAT3 to promote collagen and migration — a double paracrine wound-healing circuit.

    Evidence Keratinocyte-fibroblast co-culture, STAT3 phosphorylation, siRNA knockdown, migration assays

    PMID:23096718

    Open questions at the time
    • Whether OSM loop operates in vivo during wound healing not confirmed
    • Other keratinocyte-derived mediators in this circuit not explored
  13. 2014 Medium

    Whether FGF7 induces autophagy and how autophagy relates to keratinocyte differentiation was unknown; FGF7 was shown to stimulate mTOR-independent autophagy in keratinocytes, and BECN1/ATG5-dependent autophagy was required for FGF7-induced early differentiation (K1 expression).

    Evidence Autophagy flux assays, 3-MA and bafilomycin A1 treatment, BECN1 and ATG5 siRNA in human keratinocytes

    PMID:24577098

    Open questions at the time
    • Upstream signal connecting FGFR2b to autophagy initiation not identified
    • In vivo relevance of autophagy for FGF7-driven differentiation untested
  14. 2014 High

    How FGF7 functions outside epithelial tissues was largely unknown; in hippocampal neurons, FGF7 was found to localize selectively to inhibitory postsynaptic sites via KIF5/gephyrin-mediated microtubule transport and to organize inhibitory (not excitatory) presynaptic differentiation.

    Evidence Time-lapse live imaging of FGF7-gephyrin co-transport, dominant-negative motor protein experiments, co-localization, siRNA in hippocampal neurons

    PMID:25431136

    Open questions at the time
    • Whether FGF7 acts through FGFR2b or another receptor at synapses not determined
    • Mechanism by which FGF7 organizes presynaptic vesicle clustering not elucidated
  15. 2015 High

    The upstream signals inducing FGF7 in the intestinal niche were unknown; GLP-1 receptor signaling was shown to require FGF7 for intestinal mucosal growth, as Fgf7-/- mice failed to respond to exendin-4.

    Evidence Genetic epistasis with Fgf7-/- and Glp1r-/- mice, exendin-4 treatment, intestinal morphometry

    PMID:25738454

    Open questions at the time
    • Cell type producing FGF7 downstream of GLP-1R not definitively identified
    • Whether this pathway operates in human intestine not established
  16. 2019 High

    The mechanism by which KGF drives wound contraction was unclear; KGF was shown to stimulate keratinocyte TGF-β1 secretion, which activates fibroblast contraction via Smad2/3-dependent α-SMA and collagen I upregulation, validated by TGF-β1 neutralizing antibody in vitro and in a diabetic rat wound model.

    Evidence Keratinocyte-fibroblast co-culture, FPCL contraction, TGF-β1 ELISA, neutralizing antibody, diabetic rat wound model

    PMID:30894415

    Open questions at the time
    • Whether this loop is the dominant wound contraction mechanism versus other pathways not established
    • Diabetic-specific versus general wound context not fully dissected
  17. 2021 Medium

    Whether FGF7-FGFR2 autocrine signaling operates in cancer cells (beyond paracrine) and contributes to therapy resistance was unclear; autocrine FGF7-FGFR2 loops were demonstrated in PAX3-FOXO1 rhabdomyosarcoma sustaining MAPK and viability, and in cholangiocarcinoma where SOX9 transcriptionally drives both FGF7 and FGFR2, promoting pemigatinib resistance.

    Evidence siRNA knockdown of FGF7 and FGFR2, FGFR inhibitors, xenograft models; WNT3A-SOX9 axis mapping and FGF7 neutralizing antibody in CCA

    PMID:34850536 PMID:35428876

    Open questions at the time
    • Whether autocrine FGF7 loops are general features of FGFR2-amplified cancers not determined
    • Patient-derived validation limited
  18. 2024 Medium

    Whether FGF7 plays a paracrine role in muscle regeneration was untested; fibro-adipogenic progenitor-derived FGF7 was shown to promote muscle satellite cell proliferation via FGFR2, with FGFR2 knockdown abolishing the proliferative response.

    Evidence scRNA-seq with CellChat, EdU proliferation, FGFR2 siRNA, cardiotoxin injury and aging models in vivo

    PMID:38751367

    Open questions at the time
    • Whether FGF7 or FGF10 is the dominant FGFR2b ligand in muscle regeneration not resolved
    • Downstream signaling in satellite cells not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how the same FGFR2b receptor selectively activates different MAPK branches in different cell types; the structural basis of dermatan sulfate co-receptor function; whether FGF7's neuronal synapse-organizing function acts through FGFR2b; and the full scope of autocrine FGF7-FGFR2 signaling in therapy-resistant cancers.
  • No co-crystal structure of FGF7–dermatan sulfate–FGFR2b ternary complex
  • Mechanism of context-dependent MAPK branch selection downstream of FGFR2b not resolved
  • Receptor identity for neuronal FGF7 synapse function not confirmed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-112316 Neuronal System 1 R-HSA-9612973 Autophagy 1
Partners
CTNNB1FGFBP1FGFR2GPHNGRB2KIF5

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 KGF (FGF7) is a stromal cell-derived mitogen specific for epithelial cells, identified as a member of the FGF family by cDNA sequencing, with expression restricted to stromal cells of epithelial tissues. cDNA cloning, expression analysis Science High 2475908
1991 KGF receptor was identified as a transmembrane tyrosine kinase (FGFR2 IIIb) distinct from the basic FGF receptor, with high affinity for KGF and acidic FGF, cloned by an autocrine transformation assay in NIH/3T3 cells. Expression cDNA library cloning, receptor binding competition assay, transformation focus assay Science High 1846048
1994 KGF receptor signaling is required for normal epidermal morphogenesis and wound reepithelialization; dominant-negative KGF receptor transgene in basal keratinocytes caused epidermal atrophy, hair follicle abnormalities, and substantially delayed wound reepithelialization with reduced keratinocyte proliferation at the wound edge. Dominant-negative transgenic mouse model, histology, proliferation assay Science High 7973639
2002 Dermatan sulfate (chondroitin sulfate B), the predominant glycosaminoglycan in skin, acts as the principal co-factor for FGF7 activity; it enables FGF7-dependent FGFR2 IIIb binding, MAPK phosphorylation, and keratinocyte proliferation, whereas heparan sulfate and chondroitin sulfate A/C do not support FGF7 activity. Cell proliferation assay (BaF/KGFR lymphoid cell line), radiolabeled FGF7 receptor binding assay, MAPK phosphorylation assay, glycosaminoglycan fractionation Journal of Biological Chemistry High 12215437
2003 Structure-based mutagenesis identified specific FGF7 residues (β4/β5 loop, Asp63, Leu142, Arg65) required for exclusive binding to FGFR2IIIb; mutations in these residues reduced receptor binding affinity and biological activity. Structure-based modeling, site-directed mutagenesis, receptor binding assay, biological activity assay FEBS Letters High 14527678
2019 Structural analysis reveals that FGF7 subfamily members (FGF3, FGF7, FGF10, FGF22) achieve restricted specificity for FGFR1b/FGFR2b by engaging alternatively spliced loop regions in the immunoglobulin-like domain 3 (D3) of these receptors, with weak basal receptor-binding affinity further constraining specificity. Structural analysis, comparative receptor-binding analysis Frontiers in Genetics Medium 30809251
2005 FGF-binding protein (FGF-BP) physically interacts with FGF7, FGF10, and FGF22, and enhances the biological activity of low concentrations of these ligands; FGF-BP expression is upregulated after skin injury in keratinocytes. Co-immunoprecipitation/pulldown binding assay, in vitro activity assay, wound model Oncogene Medium 15806171
2003 KGF (FGF7) inducible expression in mouse lung activates the Akt pro-survival signaling axis in lung epithelial cells (not endothelial cells), and dominant-negative Akt blocks KGF-mediated protection from hyperoxia-induced cell death, consistent with selective KGFR expression on epithelium. Tetracycline-inducible transgenic mouse system, dominant-negative Akt mutant, in vitro and in vivo cell death assays PNAS High 12732722
2007 KGF signaling in thymic epithelial cells activates the p53 and NF-κB pathways and induces transcription of BMP2, BMP4, Wnt5b, and Wnt10b; canonical BMP signaling is critical for KGF-mediated TEC expansion and T-cell development. In vivo KGF administration, signaling pathway analysis, pathway inhibition experiments, gene expression profiling Blood Medium 17213286
2005 KGF/FGF7 induces lipogenesis in pulmonary epithelial H292 cells through a PI3K and JNK/SREBP-1 signaling pathway; KGF activates Akt, p70 S6K, JNK, and ERK; JNK and PI3K (but not ERK) are required for SREBP-1, FAS, and SCD-1 induction; SREBP-1 binding site in SCD-1 promoter is required for KGF effect. Pharmacological pathway inhibition (SP600125, LY294002, PD98059), luciferase promoter assays, dominant-negative and dominant-active SREBP-1 adenoviral constructs, Western blot Journal of Lipid Research High 16162944
2009 KGF promotes ductal cell proliferation through the MEK-ERK1/2 pathway and ductal cell differentiation (PDX1, Glut2 expression) through a PI3K/AKT-dependent mechanism in pancreatic duct cells, contributing to beta-cell neogenesis. BrdU incorporation assay, pharmacological MEK inhibition (in vitro and in vivo), morpholino antisense against MEK1, PI3K inhibition, immunolocalization PLoS ONE Medium 19266047
2007 KGF-induced retention of alveolar type II cell phenotype (preventing transdifferentiation to type I-like cells) is mediated specifically by JNK activation and downstream c-Jun phosphorylation; inhibition of JNK (but not ERK1/2 or p38) abrogates this effect, and overexpression of JNKK2 promotes AT2 phenotype markers. Primary rat AEC culture, selective MAPK inhibitors, JNKK2 overexpression, immunoblot, monoclonal antibody phenotyping American Journal of Respiratory Cell and Molecular Biology Medium 17872496
1997 KGF protects airway epithelial cells against H2O2-induced permeability increase and disruption of F-actin cytoskeleton via a PKC-dependent mechanism; calphostin C (PKC inhibitor) abolishes both the KGF-mediated decrease in basal albumin flux and protection against H2O2. Transwell permeability assay, pharmacological PKC inhibition, F-actin immunostaining American Journal of Physiology Medium 9142942
1997 KGF increases DNA repair capacity in irradiated pulmonary epithelial cells through DNA polymerases-α, -δ, and -ε (blocked by aphidicolin and butylphenyl dGTP but not dideoxythymidine triphosphate, ruling out polymerase-β). Alkaline unwinding DNA damage assay, selective DNA polymerase inhibitors American Journal of Physiology Medium 9227520
1998 KGF upregulates active Na+ transport across alveolar epithelial cell monolayers by increasing Na+/K+-ATPase α1 subunit mRNA and protein (α1 and β1 subunit protein), without increasing rENaC subunit mRNAs (which actually decrease), suggesting Na pump upregulation as the primary mechanism. Short-circuit current measurement, quantitative mRNA assay, Western blot American Journal of Physiology Medium 9458813
2009 KGF promotes limbal epithelial outgrowth by inducing ΔNp63α expression through the p38 MAPK pathway; inhibition of p38 blocks KGF-induced ΔNp63α upregulation, and knockdown of ΔNp63α significantly reduces KGF-induced outgrowth. Ex vivo limbal explant culture, kinase inhibitor studies, siRNA knockdown, immunofluorescence Journal of Cell Science Medium 19920075
2006 KGF suppresses α2β1 integrin expression and function in prostatic epithelial transient amplifying population (TAP) cells, inducing differentiation (PAP, CK18, androgen receptor expression) via p38-MAPK; p38 inhibitor (SB202190) blocks KGF-induced differentiation. Primary human prostate epithelial culture, flow cytometry, immunofluorescence, pharmacological p38 inhibition, FGFR2 expression analysis by FACS Journal of Cell Science Medium 16554439
2014 FGF7/KGF induces autophagy in human keratinocytes via a PI3K-AKT-MTOR-independent pathway, stimulating autophagosome formation; upon prolonged stimulus, FGF7 also accelerates autophagosome turnover. Autophagy is required for FGF7-mediated early differentiation (KRT1/K1 upregulation), as shown by 3-MA, BECN1, and ATG5 depletion. Quantitative fluorescence assays of autophagy, selective autophagy inhibitors (3-MA, bafilomycin A1), siRNA knockdown of BECN1 and ATG5, Western blot Autophagy Medium 24577098
2014 FGF7 localizes to inhibitory postsynaptic sites in hippocampal neurons and functions as a presynaptic organizer for inhibitory (but not excitatory) synapse differentiation; its selective inhibitory synaptic targeting requires the motor protein KIF5 and the adaptor protein gephyrin for microtubule transport, with FGF7 co-transported with gephyrin as shown by time-lapse imaging. Time-lapse live imaging, co-localization assays, dominant-negative motor protein experiments, immunofluorescence, siRNA knockdown Journal of Cell Science High 25431136
2012 Increased KGF expression induces fibroblast activation through a double paracrine loop: KGF stimulates keratinocytes to produce and secrete oncostatin M (OSM), which then activates fibroblasts (collagen I-α1 upregulation, increased migration) via OSM-regulated STAT3 phosphorylation and urokinase plasminogen activator expression. Co-culture systems, ELISA, Western blot (STAT3 phosphorylation), siRNA knockdown, migration assays Journal of Investigative Dermatology Medium 23096718
2019 KGF-1 promotes wound contraction via a double-paracrine mechanism: KGF-1 stimulates keratinocytes to secrete TGF-β1, which then activates fibroblasts to contract collagen lattices; TGF-β1 neutralizing antibody attenuates KGF-1-induced fibroblast contraction, and this involves the TGF-β1/Smad2/3 pathway with α-SMA and collagen I upregulation. Keratinocyte-fibroblast co-culture, fibroblast-populated collagen lattice (FPCL) contraction assay, ELISA (TGF-β1), Western blot (p-Smad2/3, α-SMA, Col-I), TGF-β1 neutralizing antibody, diabetic rat wound model Journal of Biological Chemistry High 30894415
2007 KGF-induced motility of breast cancer cells requires Grb2 (an adaptor protein) and ERK1/2 activation downstream of the KGF receptor tyrosine kinase; Grb2 knockdown and ERK1/2 inhibition (PD98059) suppress KGF-induced motility, whereas Akt inhibition (wortmannin) does not. Antisense/siRNA knockdown of Grb2, pharmacological ERK and Akt inhibition, wounding motility assay, cDNA microarray Clinical & Experimental Metastasis Medium 15672868
2000 IL-1α produced by prostatic epithelial cells acts as a paracrine inducer of FGF7 expression in prostatic stromal cells; blocking with anti-IL-1α antibodies or IL-1Ra abrogates the epithelial conditioned medium-induced FGF7 upregulation in stroma, establishing a double paracrine loop. Conditioned medium experiments, neutralizing antibody blocking, ELISA, immunohistochemistry American Journal of Pathology Medium 10880394
1996 KGF can replace testosterone as a paracrine mediator of ductal branching morphogenesis in rat ventral prostate; KGF is expressed in prostatic mesenchyme and its receptor exclusively in epithelium; neutralization of endogenous KGF with anti-KGF antibody or soluble KGFR inhibits androgen-stimulated growth and reduces ductal end buds. RT-PCR expression analysis, in situ hybridization, organ culture with neutralizing antibody and soluble receptor peptide, DNA content assay International Journal of Developmental Biology Medium 8946242
2015 GLP-1 receptor signaling promotes intestinal mucosal growth through FGF7; exendin-4 increases Fgf7 expression, and intestinal growth response to exendin-4 is absent in Fgf7-/- mice, placing FGF7 downstream of GLP-1R in intestinal mucosal expansion. Glp1r-/- and Fgf7-/- mouse genetic epistasis, exendin-4 treatment, gene expression analysis, intestinal morphometry Cell Metabolism High 25738454
2017 FGF7/FGFR2 signaling promotes invasion and migration of gastric cancer cells through upregulation of THBS1 (thrombospondin-1) via the PI3K/Akt/mTOR pathway; FGFR2 or THBS1 knockdown suppresses FGF7-induced invasion/migration. siRNA knockdown of FGFR2 and THBS1, invasion/migration assays, PI3K/Akt/mTOR pathway inhibitor studies, Western blot International Journal of Oncology Medium 28339036
2018 FGF7 promotes osteocyte cell processes by inducing β-catenin cytoplasmic accumulation and nuclear translocation, which increases connexin43 (Cx43) expression and gap junction formation between osteocytes. Western blot, immunofluorescence (β-catenin nuclear translocation), gap junction/cell process assays in MLO-Y4 cells Scientific Reports Medium 30287900
2021 FGF7 promotes osteoblast dendrite elongation and gap junctional intercellular communication (GJIC) by inducing E11 expression; E11 directly interacts with connexin43 (Cx43) in primary osteoblasts; MAPK and PI3K-AKT pathways are involved. Western blot, immunofluorescence, co-immunoprecipitation (E11-Cx43 interaction), GJIC functional assay, pathway inhibition International Journal of Biological Sciences Medium 34671204
2024 Fibro-adipogenic progenitors (FAPs) signal to muscle satellite cells (MuSCs) via FGF7-FGFR2; exogenous FGF7 promotes MuSC proliferation and muscle regeneration, and FGFR2 knockdown abolishes FGF7-induced proliferation. Single-cell RNA sequencing, CellChat ligand-receptor analysis, EdU proliferation assay, FGFR2 siRNA knockdown, cardiotoxin injury and d-galactose aging models in vivo Journal of Cachexia, Sarcopenia and Muscle Medium 38751367
2022 SOX9, induced by WNT3A-TCF7 signaling, transcriptionally upregulates both FGF7 and FGFR2 in cholangiocarcinoma; FGF7 is secreted and activates FGFR2 in an autocrine pathway, promoting CCA proliferation and pemigatinib resistance; neutralizing FGF7 or inhibiting HIF-1α reverses FGF7-mediated EMT. mRNA sequencing, in vitro/in vivo validation, WNT3A stimulation assays, FGF7 neutralizing antibody, HIF-1α pathway inhibition Oncogene Medium 35428876
2021 FGF7-FGFR2 autocrine signaling in fusion-gene-positive (PAX3-FOXO1) rhabdomyosarcoma sustains MAPK activity and promotes cell viability and chemoresistance; genetic silencing of FGFR2 or FGF7 decreases cell viability, and pharmacological FGFR inhibition reduces tumor growth in vivo. siRNA knockdown of FGFR2 and FGF7, MAPK activity assay, FGFR inhibitor (NVP-BGJ398), xenograft tumor model Molecular Oncology Medium 34850536
2024 CAF-derived FGF7 inhibits ubiquitination and degradation of HIF-1α via FGFR2 interaction in ovarian cancer cells, activating HIF-1α-dependent EMT; neutralizing antibodies against FGF7 substantially reduce tumor growth in vivo. Single-cell transcriptomic analysis, in vitro FGFR2 binding assays, HIF-1α ubiquitination assay, neutralizing antibody treatment, xenograft model Journal of Translational Medicine Medium 38491511
1996 The KGF/FGF7 promoter is androgen-regulated; transient transfection in LNCaP cells with the synthetic androgen R1881 upregulated KGF promoter activity 6–11-fold, with androgen-responsive elements mapping to the region -900 to -1200. Promoter-reporter transfection assay, androgen stimulation Biochemical and Biophysical Research Communications Medium 8607856
2007 KGF promotes integrin α5 expression in keratinocytes by inducing sustained ERK1/2-dependent phosphorylation of C/EBP-β transcription factor; dominant-negative C/EBP-β inhibits α5 promoter activity and C/EBP-β siRNA reduces integrin α5 expression. Promoter-reporter assay, dominant-negative C/EBP-β, siRNA knockdown, Western blot (ERK1/2, C/EBP-β phosphorylation), 3D epidermal tissue analogues American Journal of Physiology - Cell Physiology Medium 17596295
1999 In salivary gland branching morphogenesis, FGF7 and EGF produce distinct morphological outcomes: EGF induces lobule formation and cleft formation, while FGF7 promotes stalk elongation associated with differential cell proliferation (higher in distal regions); these effects correlate with spatially distinct patterns of FGFR expression. Mesenchyme-free salivary epithelial explant culture, BrdU labeling, whole-mount analysis Developmental Dynamics Medium 10373019
2003 AS101-induced hair growth is mediated by KGF; anti-KGF neutralizing antibodies and dominant-negative KGF receptor transgene abolish the AS101-induced anagen; AS101 upregulates KGF expression in fibroblasts via the Ras signaling pathway. Neutralizing antibody, dominant-negative transgenic mouse, fibroblast culture with Ras pathway analysis FASEB Journal Medium 14656992

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science (New York, N.Y.) 958 2475908
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
1994 FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial-mesenchymal interactions. Mechanisms of development 254 8186145
2006 Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood 183 17138819
2005 GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors. Regulatory peptides 178 15544847
2005 Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration. Blood 177 16304055
2007 Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells. Blood 172 17213286
1997 FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Developmental dynamics : an official publication of the American Association of Anatomists 148 9056643
1996 Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate. The International journal of developmental biology 136 8946242
1999 Lacrimal gland HGF, KGF, and EGF mRNA levels increase after corneal epithelial wounding. Investigative ophthalmology & visual science 130 10476782
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
2015 GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7. Cell metabolism 117 25738454
2017 FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. International journal of oncology 109 28339036
2002 Dermatan sulfate binds and potentiates activity of keratinocyte growth factor (FGF-7). The Journal of biological chemistry 86 12215437
2004 Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development. Development (Cambridge, England) 85 15201220
2022 Scarless wound healing: Current insights from the perspectives of TGF-β, KGF-1, and KGF-2. Cytokine & growth factor reviews 83 35690568
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 The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair. Oncogene 80 15806171
2005 KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells. Journal of lipid research 75 16162944
1999 FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. The Journal of urology 73 10411093
2004 Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model. Gene therapy 71 15470477
1997 KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells. The American journal of physiology 71 9227520
2012 Increased KGF expression promotes fibroblast activation in a double paracrine manner resulting in cutaneous fibrosis. The Journal of investigative dermatology 70 23096718
1997 KGF prevents hydrogen peroxide-induced increases in airway epithelial cell permeability. The American journal of physiology 70 9142942
2000 Interleukin-1alpha is a paracrine inducer of FGF7, a key epithelial growth factor in benign prostatic hyperplasia. The American journal of pathology 63 10880394
2019 Structural Biology of the FGF7 Subfamily. Frontiers in genetics 59 30809251
1999 EGF-dependent lobule formation and FGF7-dependent stalk elongation in branching morphogenesis of mouse salivary epithelium in vitro. Developmental dynamics : an official publication of the American Association of Anatomists 58 10373019
1998 Na(+)-K(+)-ATPase expression in alveolar epithelial cells: upregulation of active ion transport by KGF. The American journal of physiology 55 9458813
2018 miR-381-3p restrains cervical cancer progression by downregulating FGF7. Journal of cellular biochemistry 50 30161290
2004 Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN. Journal of parenteral and enteral nutrition 50 15568286
2018 The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing. Journal of tissue engineering and regenerative medicine 47 29706001
2009 The growth-promoting effect of KGF on limbal epithelial cells is mediated by upregulation of DeltaNp63alpha through the p38 pathway. Journal of cell science 46 19920075
1994 Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. Cellular & molecular biology research 46 7866434
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
1999 FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells. International journal of cancer 43 10389758
2010 Immuno-histochemical evaluation of solar lentigines: The association of KGF/KGFR and other factors with lesion development. Journal of dermatological science 42 20620021
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
2004 Accelerated wound healing by in vivo application of keratinocytes overexpressing KGF. Molecular therapy : the journal of the American Society of Gene Therapy 41 15233945
2019 Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis. Cancer management and research 40 31308741
2002 Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 39 12645668
2022 Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway. Oncogene 38 35428876
2019 KGF-1 accelerates wound contraction through the TGF-β1/Smad signaling pathway in a double-paracrine manner. The Journal of biological chemistry 38 30894415
2006 KGF suppresses alpha2beta1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium. Journal of cell science 36 16554439
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
2007 Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling. American journal of respiratory cell and molecular biology 35 17872496
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 34 32434772
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 31 27766421
2011 Noncovalent PEGylation by polyanion complexation as a means to stabilize keratinocyte growth factor-2 (KGF-2). Biomacromolecules 30 21954860
2002 Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations of estradiol. Prostate cancer and prostatic diseases 30 12496997
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
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
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 28 38751367
2011 Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease. Thorax 28 21921092
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
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
2021 Cell-subpopulation alteration and FGF7 activation regulate the function of tendon stem/progenitor cells in 3D microenvironment revealed by single-cell analysis. Biomaterials 24 34810035
1998 Keratinocyte growth factor (KGF) induces aromatase activity in cultured MCF-7 human breast cancer cells. Anticancer research 24 9703907
2024 Microneedle Patch for Transdermal Sequential Delivery of KGF-2 and aFGF to Enhance Burn Wound Therapy. Small (Weinheim an der Bergstrasse, Germany) 23 38623988
2018 Keratinocyte Growth Factor (KGF) Modulates Epidermal Progenitor Cell Kinetics through Activation of p63 in Middle Ear Cholesteatoma. Journal of the Association for Research in Otolaryngology : JARO 22 29549594
2002 Keratinocyte Growth Factor (KGF) in hematology and oncology. Current pharmaceutical design 22 12069377
2018 Hair growth is promoted by BeauTop via expression of EGF and FGF‑7. Molecular medicine reports 21 29693180
1997 Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF. The American journal of physiology 21 9316491
2024 Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter. Journal of translational medicine 20 38491511
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 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 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
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
2022 FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer. Molecular oncology 18 35726195
2019 Comparative Analysis of KGF-2 and bFGF in Prevention of Excessive Wound Healing and Scar Formation in a Corneal Alkali Burn Model. Cornea 18 31490279
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
2000 Vitamin D induced up-regulation of keratinocyte growth factor (FGF-7/KGF) in MCF-7 human breast cancer cells. Biochemical and biophysical research communications 18 10873663
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 17 37569486
2021 FGF7-induced E11 facilitates cell-cell communication through connexin43. International journal of biological sciences 17 34671204
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
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
2002 In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells. Cancer chemotherapy and pharmacology 16 12203102
1996 Keratinocyte growth factor (KGF/FGF-7) has a paracrine role in canine prostate: molecular cloning of mRNA encoding canine KGF. DNA and cell biology 16 8634153
2021 FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas. Molecular oncology 15 34850536