Affinage

FGF2

Fibroblast growth factor 2 · UniProt P09038

Round 2 corrected
Length
288 aa
Mass
30.8 kDa
Annotated
2026-04-28
130 papers in source corpus 52 papers cited in narrative 52 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF2 is a heparin-binding growth factor that signals through FGFR tyrosine kinases to drive proliferation, angiogenesis, osteogenesis, neurogenesis, and tissue repair. The single FGF2 gene produces a secreted 18-kDa (LMW) isoform initiated at an AUG codon and several nuclear high-molecular-weight (HMW) isoforms initiated at upstream CUG codons; the LMW isoform is exported by an unconventional ER/Golgi-independent mechanism involving PI(4,5)P2-mediated membrane recruitment, FGF2 oligomerization into transient pores, and heparan-sulfate capture at the outer leaflet (~200 ms kinetics), while HMW isoforms are retained in the nucleus where they regulate mRNA export through an API5-dependent interaction with TREX and eIF4E/LRPPRC complexes (PMID:30470711, PMID:32383752, PMID:2726761). Crystal structures of binary and ternary FGF2–FGFR–heparin complexes established that heparan sulfate serves as an obligate co-receptor, simultaneously augmenting FGF–FGFR binding and bridging receptor dimerization via 6-O-sulfate contacts; receptor activation requires Y653/Y654 autophosphorylation and triggers RAS/ERK, PI3K/AKT, PLCγ, and STAT3 cascades whose outputs include RUNX2-driven osteogenic and catabolic gene programs, SDF-1 induction via Erm, and miR-105/ADAMTS regulation via NF-κB (PMID:11030354, PMID:8622701, PMID:15564063, PMID:16816250). Fgf2 knockout mice exhibit reduced cortical neurogenesis, delayed wound healing, blunted PTH-induced bone formation, and enhanced brown/beige fat thermogenesis, confirming non-redundant roles in development, repair, and metabolism (PMID:9576942, PMID:10864959, PMID:34710640).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1986 High

    Cloning of human FGF2 revealed an ORF lacking a classical signal peptide, establishing that this growth factor uses an unconventional export route—a question that would take three decades to resolve mechanistically.

    Evidence cDNA cloning and sequence analysis from multiple human libraries

    PMID:3780670

    Open questions at the time
    • Mechanism of secretion completely unknown
    • Receptor identity unknown
  2. 1989 High

    Identification of CUG-initiated HMW isoforms sharing the same ORF as the AUG-initiated 18-kDa form established that a single gene produces functionally distinct nuclear and secreted proteins through alternative translation initiation.

    Evidence In vitro transcription/translation and site-directed mutagenesis of start codons in COS cells

    PMID:2538817 PMID:2726761

    Open questions at the time
    • Nuclear functions of HMW isoforms unknown
    • Whether HMW isoforms require FGFR signaling unclear
  3. 1991 High

    The crystal structure of FGF2 revealed a 12-strand β-trefoil fold and mapped heparin- and receptor-binding surfaces, providing the structural framework for understanding ligand–receptor specificity.

    Evidence X-ray crystallography of human bFGF

    PMID:1702556

    Open questions at the time
    • No co-crystal with receptor or heparin yet available
    • Mechanism of receptor dimerization unknown
  4. 1996 High

    Systematic receptor profiling and FGFR1 mutagenesis resolved two critical questions: FGF2 activates multiple FGFR splice variants with differential potency (specificity set by D3 splicing), and kinase activation absolutely requires Y653/Y654 autophosphorylation to trigger MAPK and downstream biological responses.

    Evidence BaF3 cells expressing individual FGFR variants for mitogenic assays; site-directed tyrosine mutagenesis with MAPK and PC12 differentiation readouts

    PMID:8622701 PMID:8663044

    Open questions at the time
    • Structural basis for D3-mediated specificity not yet defined
    • Role of heparin in receptor complex assembly unclear at atomic level
  5. 1999 High

    Crystal structures of binary and ternary FGF2–FGFR1–heparin complexes revealed the complete dimerization mechanism: FGF2 makes trans-contacts with the partner receptor D2 domain, and heparin simultaneously augments each FGF–FGFR pair and bridges the two receptor chains via 6-O-sulfate groups, answering how heparan sulfate functions as an obligate co-receptor.

    Evidence X-ray crystallography of 2:2 FGF2–FGFR1 and 2:2:2 FGF–FGFR–heparin ternary complexes

    PMID:10490103 PMID:10830168 PMID:11030354

    Open questions at the time
    • No structure of full-length receptor ectodomain on membrane
    • Dynamics of assembly on cell surface unknown
  6. 1998 High

    Fgf2 knockout mice revealed non-redundant in vivo functions: reduced cortical progenitor expansion with selective loss of deep-layer neurons, and delayed wound healing, establishing FGF2 as essential for neurogenesis and tissue repair despite the presence of other FGFs.

    Evidence Germline Fgf2 KO mice with histomorphometry, cell counting, and wound-healing assays

    PMID:10864959 PMID:9576942

    Open questions at the time
    • Isoform-specific contributions to phenotype unclear
    • Compensation by other FGFs not quantified
  7. 2004 High

    Downstream signaling was dissected in specific cell contexts: FGF2 activates RUNX2 via MEK/ERK to drive MMP-13 in cartilage catabolism, and induces G1 arrest through cyclin–CDK complex disassembly in chondrocytes, showing that FGF2 signaling output is highly context-dependent.

    Evidence MEK/ERK inhibitor epistasis, RUNX2 promoter reporters, cyclin–CDK co-IP in chondrocytes

    PMID:15194433 PMID:15564063

    Open questions at the time
    • In vivo cartilage relevance not tested with isoform-specific models
    • Direct phosphorylation sites on RUNX2 by ERK not mapped
  8. 2008 High

    Discovery that caspase-1 physically interacts with FGF2 and is required for its unconventional secretion linked inflammatory signaling to FGF2 export, though the translocation mechanism remained unresolved.

    Evidence Secretome iTRAQ proteomics, co-immunoprecipitation, brefeldin-A insensitivity controls

    PMID:18329368

    Open questions at the time
    • Caspase-1 is not the protease acting on FGF2—its mechanistic role unclear
    • Membrane translocation step undefined
  9. 2018 High

    Single-molecule TIRF imaging resolved the long-standing secretion question: individual FGF2 translocation events last ~200 ms, require PI(4,5)P2-mediated inner-leaflet recruitment and heparan-sulfate capture at the outer leaflet, and proceed through FGF2 dimer-seeded oligomeric membrane pores. Concurrently, isoform-specific KO mice demonstrated that LMW and HMW FGF2 have opposing roles in joint homeostasis.

    Evidence Live-cell single-molecule TIRF microscopy with dual-channel imaging; isoform-specific Fgf2 KO mice with mechanical OA induction

    PMID:30144364 PMID:30470711

    Open questions at the time
    • Pore stoichiometry and lipid composition requirements not fully defined
    • Whether PKCε and caspase-1 act on the same or sequential steps unclear
  10. 2020 High

    The nuclear function of FGF2 was structurally defined: API5 recognizes a cryptic NLS in FGF2, and the crystal structure of the API5–FGF2 complex showed how nuclear FGF2 regulates mRNA export through TREX and eIF4E/LRPPRC pathways, controlling c-MYC and cyclin D1 mRNAs.

    Evidence X-ray crystallography of API5–FGF2 complex, site-directed mutagenesis, mRNA export assays

    PMID:32383752

    Open questions at the time
    • Genome-wide mRNA targets of nuclear FGF2 not defined
    • Whether HMW-specific N-terminal extensions contribute to TREX interaction unclear
  11. 2023 High

    Transcriptional regulation of FGF2 itself was clarified: hypoxia-induced lactylation of YY1 at K183 (by p300) drives FGF2 transcription to promote retinal neovascularization, and VEGF-B was identified as an endogenous FGF2 antagonist that sequesters FGFR1 into an FGFR1/VEGFR1 heterodimer.

    Evidence Lactylation proteomics, ChIP for YY1 at FGF2 promoter, K183 mutant; FGFR1/VEGFR1 co-IP and in vivo tumor models

    PMID:37085894 PMID:37591843

    Open questions at the time
    • Whether other lactylation writers besides p300 regulate YY1–FGF2 axis unknown
    • Stoichiometry and affinity of FGFR1/VEGFR1 heterocomplex not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full stoichiometry and lipid requirements of the FGF2 translocation pore, the genome-wide RNA targets of nuclear HMW FGF2, how the multiple extracellular modulators (PTX3, VEGF-B, AGR2, CCN2, heparanase) are integrated in vivo, and whether isoform-specific functions explain the context-dependent pro-proliferative versus growth-arrest outcomes of FGF2 signaling.
  • Pore composition and reconstitution in synthetic membranes not achieved
  • No systematic identification of nuclear FGF2 RNA targets
  • In vivo integration of multiple extracellular FGF2 modulators untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0008289 lipid binding 2
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1430728 Metabolism 1
Partners
AGR2API5CASP1CCN2FGFR1FGFR2FGFR3PTX3
Complex memberships
API5–FGF2 nuclear complexFGF2–FGFR1–heparin ternary signaling complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 Human basic FGF (FGF2) was cloned from multiple human cDNA libraries; nucleotide sequencing revealed a single FGF2 gene encoding a protein with 99% homology to bovine bFGF and lacking a classical signal peptide sequence, suggesting unconventional secretion and intracellular storage. cDNA cloning, genomic Southern blot, sequence analysis The EMBO journal High 3780670
1989 The human FGF2 gene encodes four polypeptides (17.8, 22.5, 23.1, and 24.2 kDa); the 17.8-kDa form initiates at an AUG codon, while the three higher-molecular-weight forms initiate translation at upstream non-AUG (CUG) codons within the same open reading frame. In vitro transcription/translation, site-directed mutagenesis of start codons, cell transfection, SDS-PAGE Proceedings of the National Academy of Sciences of the United States of America High 2538817 2726761
1989 High-molecular-weight forms of FGF2 (22.5 and 21 kDa) are initiated by CUG start codons upstream of the canonical AUG, and these HMW forms are as biologically active as the 18-kDa form when expressed in COS cells. In vitro mutagenesis, COS cell transfection, biological activity assay Proceedings of the National Academy of Sciences of the United States of America High 2538817
1991 The three-dimensional crystal structure of human basic FGF2 was determined, revealing a fold of 12 antiparallel beta-strands with approximate threefold internal symmetry, topologically similar to interleukin-1β; structural locations of heparin- and receptor-binding sequences were identified. X-ray crystallography Science (New York, N.Y.) High 1702556
1990 FGF2 binds with high affinity (Kd ~2–15 × 10⁻¹¹ M) to two distinct receptor tyrosine kinases (flg/FGFR1 and bek/FGFR2), each containing three extracellular immunoglobulin-like domains and an intracellular tyrosine kinase domain. cDNA cloning, NIH 3T3 cell transfection, direct radiolabeled ligand-binding and Scatchard analysis The EMBO journal High 1697263
1996 FGF2 activates FGFR1c, FGFR2b, FGFR2c, FGFR3c, and FGFR4 with differential mitogenic potency; receptor specificity across the FGF family is determined by both the ligand and the alternatively spliced D3 domain of the receptor. Engineered BaF3 cell lines expressing individual FGFR splice variants, mitogenic proliferation assays with all nine known FGFs The Journal of biological chemistry High 8663044
1996 FGFR1 autophosphorylates on seven tyrosines upon FGF2-induced activation; phosphorylation of Y653 and Y654 is essential for kinase activation and downstream biological responses (MAPK activation, mitogenesis, neuronal differentiation), whereas phosphorylation of Y463, Y583, Y585, and Y730 is dispensable for these responses. Site-directed mutagenesis of each tyrosine, immune-complex kinase assays, MAPK activation assays, PC12 differentiation assays Molecular and cellular biology High 8622701
1997 Crystal structures of the FGFR1 tyrosine kinase domain bound to two oxindole inhibitors revealed the ATP-binding site and showed that more specific inhibitors induce a conformational change in the nucleotide-binding loop; these structures defined the structural basis for selective FGFR1 inhibition. X-ray crystallography of FGFR1 kinase domain–inhibitor complexes Science (New York, N.Y.) High 9139660
1999 The crystal structure of FGF2 bound to FGFR1 (D2–D3) at 2.8 Å resolution revealed that two FGF2:FGFR1 complexes dimerize through FGF2–D2 trans-contacts and a direct D2–D2 receptor interaction, with a positively charged canyon identified as the heparin-binding site. X-ray crystallography of FGF2–FGFR1 binary complex Cell High 10490103
2000 Crystal structure of a 2:2:2 FGF:FGFR:heparin ternary complex at 3 Å revealed that heparin plays a dual role: augmenting FGF–FGFR binding within each 1:1 complex and bridging FGFR dimerization across complexes via its 6-O-sulfate groups. X-ray crystallography of ternary FGF–FGFR–heparin complex Molecular cell High 11030354
2000 Crystal structures of FGF1–FGFR1 and FGF2–FGFR2 complexes identified a conserved FGF–D2 and FGF–linker binding interface common to all FGF–FGFR pairs, while specificity is determined by interactions between the N-terminal/central FGF regions and alternatively spliced loop regions in D3. X-ray crystallography of two FGF–FGFR binary complexes Cell High 10830168
1998 FGF2 knockout mice (lacking all three isoforms) are viable but exhibit significant reduction in neocortical neuron density (particularly layer V motor cortex) and delayed excisional skin wound healing, demonstrating non-redundant in vivo roles for FGF2 in cortical neurogenesis and wound repair. Homologous recombination knockout in ES cells, histology, immunohistochemistry, wound-healing assays in vivo Proceedings of the National Academy of Sciences of the United States of America High 9576942
2000 Fgf2 knockout mice show a 50% reduction in founder cells of the dorsal pseudostratified ventricular epithelium (cerebral cortical anlage) and a 45% decrease in cortical neuron number by end of neurogenesis, with selective loss of large deep-layer neurons, demonstrating FGF2 is required for progenitor expansion and generation of a specific cortical neuron class. Fgf2 germline knockout mice, volumetric analysis, cell counting, TUNEL apoptosis assay, in situ hybridization The Journal of neuroscience High 10864959
2008 FGF2 secretion is unconventional (ER/Golgi-independent) and depends on active caspase-1; although FGF2 is not a caspase-1 substrate, it physically interacts with caspase-1, linking inflammation-induced caspase-1 activation to FGF2 export. Secretome iTRAQ proteomics, co-immunoprecipitation, caspase-1 activity assays, brefeldin-A insensitivity controls Cell High 18329368
2009 High-molecular-weight FGF2 isoforms (initiated from CUG codons) are retained in the nucleus and act independently of cell-surface FGF receptors, while the 18-kDa LMW isoform is secreted and acts through receptor tyrosine kinases; the two classes have distinct intracellular trafficking. Isoform-specific expression constructs, immunofluorescence/fractionation, FGFR inhibition studies (review consolidating experimental data) Cellular and molecular life sciences : CMLS Medium 18850066
2018 Individual FGF2 membrane translocation events were directly visualized using live-cell TIRF microscopy; translocation required PI(4,5)P2-mediated recruitment at the inner leaflet and heparan sulfate capture at the outer leaflet, had an average duration of ~200 ms, and involved FGF2 dimers as the predominant oligomeric species at the inner leaflet, consistent with dimer-seeded higher oligomers forming membrane pores as translocation intermediates. Live-cell TIRF microscopy, single-molecule imaging, simultaneous dual-channel imaging of inner- and outer-leaflet FGF2, pharmacological/genetic manipulation of PI(4,5)P2 and heparan sulfate The Journal of cell biology High 30470711
2020 Nuclear FGF2 (18 kDa isoform) physically interacts with API5; the crystal structure of the API5–FGF2 complex identified critical interface residues and revealed a cryptic nuclear localization sequence in FGF2 explaining its nuclear import without a canonical NLS. This complex regulates mRNA nuclear export through both the TREX complex and the eIF4E/LRPPRC pathway, controlling bulk mRNA and specific mRNAs (c-MYC, cyclin D1). X-ray crystallography of API5–FGF2 complex, site-directed mutagenesis, co-immunoprecipitation, mRNA export assays, eIF4E sensitivity element reporter assays Nucleic acids research High 32383752
2004 FGF2 induces G1 growth arrest in RCS chondrocytes by activating the Ras/ERK pathway; at the molecular level, FGF2 causes disintegration of the cyclin D3–CDK6 complex, increased association of p21(WAF1) and p27(Kip1) with cyclin–CDK2 and cyclin–CDK4 complexes, and underphosphorylation of p107/p130 pocket proteins, leading to cell cycle arrest. Chemical inhibition of FGFR3 and MEK1/2, dominant-negative and constitutively active Ras expression, cyclin–CDK co-immunoprecipitation, Western blot for cell-cycle regulators Experimental cell research High 15194433
2007 FGF2 triggers PDGFR-α and PDGFR-β expression at the transcriptional level in endothelial cells, enabling them to respond to PDGF-BB; reciprocally, PDGF-BB upregulates FGFR1 promoter activity in vascular smooth muscle cells, creating a reciprocal signaling loop that drives disorganized tumor neovascularization and metastasis. Simultaneous tumor cell overexpression of PDGF-BB and FGF2, FGFR1 promoter reporter assays, in vivo fibrosarcoma models, quantitative vessel and pericyte analysis The Journal of clinical investigation High 17909625
2004 FGF2 activates RUNX2 via the MEK/ERK pathway (resulting in ~2-fold increased RUNX2 phosphorylation) in articular chondrocytes; activated RUNX2 then drives MMP-13 promoter activity and MMP-13 expression, a mechanism relevant to osteoarthritis progression. MEK/ERK inhibition, RUNX2 overexpression constructs, MMP-13 promoter reporter assays, immunohistochemistry, phospho-RUNX2 Western blot Osteoarthritis and cartilage High 15564063
2011 CCN2 (CTGF) directly binds FGF2 through its C-terminal (CT) module with a Kd of 5.5 nM (measured by surface plasmon resonance); this interaction suppresses FGF2-induced ERK1/2, p38 MAPK, and JNK phosphorylation and nullifies FGF2-driven chondrocyte proliferation and MMP-9/MMP-13 production. CCN2 full-length also binds FGFR1 (Kd 362 nM), whereas the CT module alone does not. Solid-phase binding assay, co-immunoprecipitation, surface plasmon resonance, phospho-MAPK Western blot, proliferation assays Endocrinology High 21914781
2011 Chlamydia trachomatis co-opts FGF2 signaling by (i) using FGF2 as a bridging molecule to interact with FGFR on host cells in an HSPG-dependent manner to enhance bacterial uptake, (ii) stimulating fgf2 transcription and FGF2 secretion via Erk1/2-dependent but FGFR-independent signaling, and (iii) causing proteasome-mediated degradation of HMW FGF2 isoforms while increasing LMW isoform release. FGF2 neutralization, FGFR inhibition, siRNA knockdown, Erk1/2 inhibition, proteasome inhibitor studies, conditioned medium infectivity assays, in vivo mouse model PLoS pathogens High 21998584
2013 FGF2 stimulates osteogenic differentiation by inducing TAZ mRNA expression through ERK activation; nuclear TAZ then interacts with RUNX2 to activate RUNX2-mediated osteogenic gene transcription. TAZ knockdown blocks FGF2-mediated osteogenesis. ERK inhibitor, shRNA knockdown of TAZ, TAZ–RUNX2 co-immunoprecipitation, nuclear localization immunofluorescence, osteogenic differentiation assays Bone Medium 24125755
2014 Nuclear FGF2 (in pancreatic stellate cells) and FGFR1 co-localize to the nucleus at the invasive front of human pancreatic cancer; RNAi or chemical inhibition of FGFR1 relocates FGF2 and FGFR1 to the cytoplasm, reduces PSC proliferation, and abolishes cancer cell invasion in organotypic co-cultures, demonstrating that nuclear FGF2/FGFR1 mediates PSC-driven tumor invasion. RNAi knockdown, FGFR chemical inhibition, immunofluorescence localization, organotypic invasion assays, human tumor tissue immunohistochemistry EMBO molecular medicine High 24503018
2014 API5 confers tumor immune escape by upregulating FGF2 signaling through a FGFR1/PKCδ/ERK pathway that triggers degradation of the pro-apoptotic molecule BIM; blockade of FGF2, PKCδ, or ERK phenocopies API5 silencing, restoring T-cell-mediated tumor killing. RNAi silencing, overexpression, FGF2/PKCδ/ERK pharmacological inhibition, antigen-specific T-cell killing assays, BIM protein measurement Cancer research High 24769442
2006 FGF2 is required for maximum bone anabolic response to parathyroid hormone (PTH): Fgf2−/− mice show significantly blunted PTH-induced bone formation and BMD increase compared to wild-type, and PTH-treated Fgf2−/− mice have reduced serum IGF-1, placing FGF2 in the PTH anabolic signaling pathway. Fgf2 knockout mice (Fgf2+/+, +/−, −/−), PTH administration, micro-CT, histomorphometry, DEXA, serum IGF-1 measurement Biochemical and biophysical research communications Medium 16455048
2006 Heparanase (HPSE) modulates FGF2 signaling by remodeling heparan sulfate chains: low concentrations of HPSE enhance FGF2 binding and enable ERK and FAK phosphorylation in response to FGF2 (which otherwise fails to signal), while extensive HPSE degradation inhibits FGF2 binding, demonstrating that heparan sulfate chain length/sulfation state gates FGF2–FGFR signaling competence. FGF2 binding assays, phospho-ERK and phospho-FAK Western blots, HPSE dose-response, soluble HS competition, in vivo melanoma angiogenesis assays Neoplasia (New York, N.Y.) Medium 16867222
2009 PTX3 (long pentraxin-3) binds FGF2 with high affinity and specificity, competing with FGF2's cognate tyrosine kinase receptors, thereby acting as an endogenous FGF2 antagonist that inhibits FGF2-induced angiogenesis in vitro and in vivo; the FGF2-binding domain was mapped to PTX3's N-terminal extension. Direct binding assays, receptor competition assays, in vitro and in vivo angiogenesis assays, N-terminal peptide mapping European cytokine network Medium 20167562
2013 PKCε activation promotes FGF2 export to the plasma membrane (unconventional exocytosis) and induces FGF2/FGFR1 autocrine signaling (ERK1/2 and STAT3 phosphorylation, de novo FGF2 synthesis); PKCε activation fails in FGF2−/− cells or when exocytosis is blocked by methylamine, positioning PKCε upstream of FGF2 membrane export. Selective PKCε agonist (ψεRACK), cell-surface biotinylation, immunofluorescence, FGF2−/− cells, methylamine exocytosis block, in vivo rabbit cornea angiogenesis assay Journal of molecular and cellular cardiology Medium 23880610
2017 Secreted AGR2 directly binds FGF2 and promotes FGF2 homodimerization, enhancing FGF2 angiogenic activity; an anti-AGR2 monoclonal antibody targeting the AGR2 self-dimerization region blocked FGF2 activation, suppressed tumor growth, and showed additive inhibition when combined with bevacizumab. Direct binding assays (co-IP, pulldown), dimerization assays, endothelial invasion assays, in vitro and in vivo tumor growth, neutralizing monoclonal antibody studies Oncogene Medium 28481872
2017 FGF2 interacts with integrin αvβ3 through residues Lys-119/Arg-120 and Lys-125; integrin-binding defective FGF2 mutants (K119E/R120E and K125E) are defective in ERK1/2 activation and DNA synthesis and act as dominant-negative antagonists suppressing WT FGF2-induced angiogenesis in tube formation, aorta ring, and in vivo assays. Site-directed mutagenesis, integrin-binding assays, ERK1/2 phosphorylation, DNA synthesis assays, tube formation, aorta ring sprouting, in vivo angiogenesis Bioscience reports Medium 28302677
2017 FGF2 regulates cytoglobin (CYGB) gene expression in hepatic stellate cells via a JNK/c-JUN pathway: FGF2 triggers rapid JNK and c-JUN phosphorylation, and phospho-c-JUN binds a consensus motif at −218 to −222 bp in the CYGB promoter to drive CYGB transcription, concomitantly reducing α-SMA expression and promoting HSC deactivation. JNK inhibitor, c-JUN siRNA/overexpression, chromatin immunoprecipitation (ChIP), CYGB promoter mapping, in vivo bile-duct ligation model with FGF2 administration The Journal of biological chemistry High 28916723
2019 FGF2 stimulation of PC12 cells activates ERK through a network involving intracellular FGFR feedback and competition between FGFRs and heparan sulfate proteoglycan (HSPG) co-receptors for FGF2 binding, producing a dose-dependent shift in the distribution of transient vs. sustained single-cell ERK states; Bayesian model selection identified HSPG competition as a key circuit element. Microfluidics-controlled FGF2 stimulation, single-cell live ERK biosensor imaging, Bayesian parameter inference, pharmacological HSPG and FGFR perturbations Molecular systems biology Medium 31777174
2018 Ablation of the LMW FGF2 isoform (Fgf2LMWKO) accelerates murine osteoarthritis with catabolic cartilage changes and increased FGFR1 expression, while ablation of HMW FGF2 isoforms (Fgf2HMWKO) protects against OA even under mechanical induction, associated with increased FGFR3 expression in cartilage; demonstrating opposing isoform-specific roles in joint homeostasis. Isoform-specific Fgf2 knockout mice, mechanical OA induction, micro-CT, histomorphometry, gene expression profiling Journal of cellular physiology High 30144364
2014 FGF2 in the bone marrow microenvironment promotes CML cell resistance to imatinib specifically through the FGFR3/RAS/c-RAF/MAPK pathway; this resistance is overcome by ponatinib (a multikinase inhibitor targeting both BCR-ABL and FGFR), and clinical FGF2 bone marrow levels decrease upon ponatinib response, validating the pathway in patients. In vitro FGF2 resistance assays, pathway inhibitor studies, clinical immunohistochemistry of bone marrow FGF2, patient cohort correlation with ponatinib response Blood Medium 24408322
2014 FGF2 promotes cten expression through MEK-ERK and PI3K-AKT signaling; upregulated cten is required for FGF2-mediated cell migration, as cten silencing blocks FGF2-induced migration while cten overexpression phenocopies FGF2 stimulation and occludes further FGF2 enhancement. Signaling pathway inhibitors, siRNA knockdown of cten, cten overexpression, cell migration assays (wound healing, transwell) Molecular carcinogenesis Medium 23625726
2009 FGF2 stimulates SDF-1 expression in Sertoli cells through the Ets transcription factor Erm; FGF2 upregulates Erm via FGFR4 (expressed in TM4 Sertoli cells but not ST2 stromal cells), and Erm directly binds the EBS at −846 to −851 of the Sdf-1 promoter to drive transcription. siRNA knockdown of Erm, FGFR subtype blocking antibody, Sdf-1 promoter reporter assay, EMSA for Erm–EBS interaction, FGF2 treatment of TM4 and ST2 cells Journal of cellular physiology Medium 19301256
2021 In glioblastoma, radiation-induced YAP nuclear translocation directly promotes FGF2 transcription (FGF2 is a novel YAP target gene); secreted FGF2 then activates MAPK-ERK signaling to promote DNA damage repair and radioresistance; YAP-FGF2-MAPK inhibition sensitizes gliomas to radiotherapy and prolongs survival in intracranial xenograft models. YAP overexpression/knockdown, ChIP for YAP at FGF2 promoter, FGF2 rescue experiments, ERK inhibition, intracranial patient-derived xenograft models with radiation Oncogene Medium 34127812
2023 Under hypoxia, the transcription factor YY1 is lactylated at K183 (regulated by the acetyltransferase p300); lactylated YY1 directly binds the FGF2 promoter to enhance FGF2 transcription, promoting retinal neovascularization; K183 mutation abolishes these effects and p300 inhibitor A485 suppresses vascularization in vivo. Lactylation proteomics (77 sites on 67 proteins identified), ChIP for YY1 at FGF2 promoter, K183 point mutant of YY1, p300 overexpression/inhibition, in vitro and in vivo OIR model Genome biology High 37085894
2023 VEGF-B acts as an endogenous inhibitor of FGF2/FGFR1-driven angiogenesis by directly binding FGFR1 and inducing formation of an FGFR1/VEGFR1 heterodimeric complex that suppresses FGF2-induced ERK activation and FGF2-driven angiogenesis and tumor growth. In vitro binding assays, FGFR1/VEGFR1 co-immunoprecipitation, ERK phosphorylation assays, in vivo angiogenesis and tumor growth models with VEGF-B gain/loss of function Signal transduction and targeted therapy Medium 37591843
2014 FGF2 induces satellite cell activation by opening TRPC1 channels to increase intracellular calcium, which drives nuclear translocation of NFATc3 and NFATc2 and increases MyoD-positive cell numbers; TRPC channel blocker SKF96365 attenuates all these FGF2-induced effects. Immunostaining for TRPC1, calcium imaging with X-rhod-1 in CD34-labeled satellite cells on isolated muscle fibers, NFATc2/3 nuclear translocation imaging, MyoD+ cell counting, TRPC pharmacological inhibition Frontiers in physiology Medium 24575047
2022 In nasopharyngeal carcinoma, tumor cell–derived FGF2 activates pericyte FGFR1/AHR signaling, driving pericyte-specific CXCL14 expression; pericyte-derived CXCL14 recruits and polarizes macrophages toward M2 phenotype (TAMs), promoting metastasis; FGF2 knockdown or pericyte depletion blocks CXCL14 and TAM infiltration. Gain- and loss-of-function of FGF2/FGFR1, genetic pericyte depletion, CXCL14 expression analysis, macrophage polarization assays, clodronate liposome macrophage depletion, xenograft metastasis models JCI insight Medium 35439170
2021 FGF2 gene disruption in mice increases thermogenic capacity of brown and beige fat (elevated UCP1, enhanced cold-tolerance); mechanistically, FGF2 acts in autocrine/paracrine fashion to suppress both PGC-1α and PPARγ expression, thereby inhibiting UCP1 transcription; this suppression was confirmed by exogenous FGF2 treatment of brown/beige adipocytes. FGF2 KO mice (chow and HFD), UCP1 expression, respiratory exchange ratio measurement, cold exposure, exogenous FGF2 treatment, Co-IP, ChIP, luciferase reporter assays for PGC-1α and PPARγ Molecular metabolism Medium 34710640
2019 In breast cancer, estrogen/GPER signaling in cancer-associated fibroblasts (CAFs) upregulates FGF2 secretion via EGFR/ERK/c-fos/AP-1 cascade; secreted FGF2 then activates FGFR1 in MDA-MB-231 cancer cells, inducing CTGF expression and promoting cancer cell migration and invasion through a paracrine FGF2/FGFR1 feedforward loop. qPCR, Western blot, ELISA, ChIP, CRISPR/Cas9 FGFR1 knockout in cancer cells, conditioned medium transfer experiments, migration/invasion assays Cells Medium 30866584
2020 FGF2 induces Connexin-43 hemichannel (Cx43 HC) opening in tanycytes, causing ATP release into the extracellular milieu; extracellular ATP then activates P2Y1 receptors to drive tanycyte proliferation; Cx43 HC blockers or P2Y1 receptor inhibitors prevent FGF2-induced β-tanycyte proliferation both in vitro and in vivo (intra-third-ventricle infusion in rats). BrdU incorporation, Cx43 HC inhibitor pharmacology, ATP release measurement, P2Y1 receptor antagonists, in vivo FGF2 + Cx43 HC inhibitor co-infusion into third ventricle Journal of neurochemistry Medium 32936929
2001 TGFβ2 and FGF2 cooperate with LIF to induce nephrogenesis in isolated metanephric mesenchyme; the inductive response is abrogated by the Wnt antagonist sFRP1 and accompanied by nuclear activation of Tcf1/Lef1, placing FGF2 upstream of a Wnt-dependent mechanism in kidney tubule formation. Rat metanephric mesenchyme explant culture, neutralizing sFRP1 protein, Tcf1/Lef1 nuclear activation assay, tubule quantification Development (Cambridge, England) Medium 11245570
2005 FGF2 treatment of developing calvarial bone stimulates Bmp2 gene expression, while Runx2 gene disruption abolishes Bmp2 expression without affecting Fgf2; Runx2-deficient cells show markedly reduced Bmp2 that is rescued and amplified by Runx2 transfection plus FGF2 treatment, placing Runx2 as an obligate mediator downstream of FGF2 in the FGF2→Runx2→Bmp2→Dlx5/Msx2 axis during cranial bone development. Runx2−/− mice, Runx2 expression plasmid transfection, FGF2 treatment of primary bone cells and MC3T3-E1 cells, Bmp2/Dlx5/Msx2 expression analysis Developmental dynamics Medium 15765505
2012 HoxA10 directly activates the FGF2 promoter via two cis-elements in myeloid progenitors; HoxA10-driven FGF2 secretion stimulates autocrine PI3K-dependent β-catenin accumulation and progenitor proliferation, identifying FGF2 as a HoxA10 target gene mediating progenitor expansion. Promoter reporter assays, ChIP for HoxA10 at FGF2 promoter, ELISA for FGF2 secretion, PI3K inhibition, β-catenin Western blot, proliferation assays The Journal of biological chemistry Medium 22493287
2010 PGF2α induces osteoblast proliferation via endogenous FGF2 in a FGFR1-dependent manner: PGF2α activates Ras and MAP-kinase, increases Bcl-2, c-Myc, MDM2, and cyclins D/E in Fgf2+/+ but not Fgf2−/− osteoblasts; neutralizing secreted FGF2 or silencing FGFR1 blocks these effects, demonstrating autocrine FGF2 as the mediator. Fgf2 KO calvarial osteoblasts, FGF2 neutralizing antibody, FGFR1 siRNA silencing, Ras activity assay, phospho-MAPK and cell cycle protein Western blots Journal of cellular physiology Medium 20432442
2015 FGF2 and IL-17 synergistically induce epithelial repair genes; Act1 (adaptor in IL-17 signaling) suppresses FGF2-induced ERK activation by binding GRB2 and preventing GRB2 association with SOS1; when IL-17 receptor engages Act1, Act1 is sequestered at the receptor complex, releasing its inhibition of FGF2/GRB2/SOS1 signaling and enabling synergistic tissue repair. Co-immunoprecipitation of Act1–GRB2 and GRB2–SOS1, Act1 KO mice, FGF2/IL-17 deficiency mouse models, DSS colitis model, gene expression analysis Immunity High 26320657
2016 FGF2 suppresses miR-105 transcription by recruiting the NF-κB subunit p65 to the miR-105 promoter; loss of miR-105 allows Runx2 (a direct miR-105 target) to accumulate, driving ADAMTS4/5/7/12 expression and aggrecan/collagen degradation in osteoarthritic cartilage. miRNA microarray, miR-105 mimic/inhibitor, Runx2 3′-UTR luciferase reporter, ChIP for p65 at miR-105 promoter, siRNA knockdown of Runx2, OA patient tissue correlation Journal of molecular medicine (Berlin, Germany) Medium 26816250
2015 Endothelial mTORC2 (Rictor) is essential for sustained FGF2-induced neovascularization: Rictor knockout in endothelium prevents FGF2-driven capillary remodeling, hemorrhagic neovascularization in Matrigel plugs, and capillary network formation in vitro; high-dose FGF2 induces Rictor expression and mTORC2-specific PKCα and AKT phosphorylation, placing mTORC2 downstream of FGF2 in extensive angiogenesis. Endothelium-specific Rictor conditional KO (embryonic and adolescent), FGF2 Matrigel plug assay, in vitro aortic endothelial cell network formation, Western blot for phospho-PKCα and phospho-AKT Scientific reports Medium 26635098

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 1447 17086194
1996 Receptor specificity of the fibroblast growth factor family. The Journal of biological chemistry 1425 8663044
2001 Fibroblast growth factors. Genome biology 1360 11276432
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2006 Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. The Journal of biological chemistry 974 16597617
2000 Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Molecular cell 958 11030354
1997 Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science (New York, N.Y.) 954 9139660
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2008 Active caspase-1 is a regulator of unconventional protein secretion. Cell 702 18329368
1990 Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. The EMBO journal 673 1697263
2007 Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 659 17981115
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1986 Human basic fibroblast growth factor: nucleotide sequence and genomic organization. The EMBO journal 591 3780670
1991 FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. The EMBO journal 553 1709094
1994 Synergy between basic fibroblast growth factor and HIV-1 Tat protein in induction of Kaposi's sarcoma. Nature 518 7935812
1989 Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proceedings of the National Academy of Sciences of the United States of America 511 2726761
1999 Structural basis for FGF receptor dimerization and activation. Cell 494 10490103
1989 High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proceedings of the National Academy of Sciences of the United States of America 472 2538817
1998 Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2. Proceedings of the National Academy of Sciences of the United States of America 471 9576942
2008 PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 463 18332228
1998 Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. The Journal of biological chemistry 425 9553078
2003 The role of PI3K in immune cells. Nature immunology 391 12660731
1997 HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region. AIDS (London, England) 374 9342064
1995 CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. The Journal of cell biology 374 7532176
1991 Three-dimensional structures of acidic and basic fibroblast growth factors. Science (New York, N.Y.) 362 1702556
2000 Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 343 10864959
1996 Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Molecular and cellular biology 342 8622701
2000 Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell 335 10830168
2007 Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. The Journal of clinical investigation 244 17909625
2004 Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis and cartilage 243 15564063
2023 YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. Genome biology 236 37085894
1997 Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain research 201 9295187
2015 Growth Factor FGF2 Cooperates with Interleukin-17 to Repair Intestinal Epithelial Damage. Immunity 193 26320657
2016 Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies. Oncotarget 154 27007053
2016 MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nature microbiology 130 27572168
2014 Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion. EMBO molecular medicine 128 24503018
2001 TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis. Development (Cambridge, England) 127 11245570
2009 A new role for FGF2 as an endogenous inhibitor of anxiety. The Journal of neuroscience : the official journal of the Society for Neuroscience 126 19439615
1997 Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas. Oncogene 118 9285563
2009 Inflammatory cells and chemokines sustain FGF2-induced angiogenesis. European cytokine network 115 19541589
2016 miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell death & disease 107 27362808
1998 Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2. Glia 91 9537840
2005 Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development. Developmental dynamics : an official publication of the American Association of Anatomists 90 15765505
2013 Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding. PloS one 87 23437109
2005 Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell organization. Biomaterials 87 15941581
2007 Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles. Journal of cellular and molecular medicine 84 18205708
2010 Characterization of tunable FGF-2 releasing polyelectrolyte multilayers. Biomacromolecules 83 20690713
2006 FGF2 binding, signaling, and angiogenesis are modulated by heparanase in metastatic melanoma cells. Neoplasia (New York, N.Y.) 74 16867222
1999 FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. The Journal of urology 73 10411093
2000 Programmed cell death in the developing heart: regulation by BMP4 and FGF2. Developmental dynamics : an official publication of the American Association of Anatomists 70 10767083
2014 MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2. Experimental & molecular medicine 69 25190353
2013 FGF2 stimulates osteogenic differentiation through ERK induced TAZ expression. Bone 66 24125755
2009 Anti-FGF2 approaches as a strategy to compensate resistance to anti-VEGF therapy: long-pentraxin 3 as a novel antiangiogenic FGF2-antagonist. European cytokine network 64 20167562
2006 Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice. Biochemical and biophysical research communications 64 16455048
2016 miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage. Journal of molecular medicine (Berlin, Germany) 63 26816250
2004 FGF2 inhibits proliferation and alters the cartilage-like phenotype of RCS cells. Experimental cell research 62 15194433
2022 FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis. JCI insight 61 35439170
2005 FGF-2, IL-1beta and TGF-beta regulate fibroblast expression of S100A8. The FEBS journal 61 15943814
2015 miR-195 Inhibits EMT by Targeting FGF2 in Prostate Cancer Cells. PloS one 58 26650737
2009 High molecular weight FGF2: the biology of a nuclear growth factor. Cellular and molecular life sciences : CMLS 58 18850066
2017 Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization. Oncogene 57 28481872
2008 FGF-2 enhances vascularization for adipose tissue engineering. Plastic and reconstructive surgery 55 18349632
2019 GPER Mediates a Feedforward FGF2/FGFR1 Paracrine Activation Coupling CAFs to Cancer Cells toward Breast Tumor Progression. Cells 53 30866584
2007 Creating a neurogenic environment: the role of BDNF and FGF2. Molecular and cellular neurosciences 52 17656107
2023 VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal transduction and targeted therapy 51 37591843
2011 Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. PLoS pathogens 51 21998584
2011 HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells. Cancer research 50 21266348
2009 Retinal expression of Fgf2 in RCS rats with subretinal microphotodiode array. Investigative ophthalmology & visual science 46 19264883
2014 API5 confers tumoral immune escape through FGF2-dependent cell survival pathway. Cancer research 45 24769442
1997 Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth. Current eye research 45 9088738
2017 The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis. Bioscience reports 44 28302677
2014 Systemic administration of fibroblast growth factor-2 (FGF2) reduces BACE1 expression and amyloid pathology in APP23 mice. Neurobiology of aging 44 25457554
2011 Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes. Endocrinology 44 21914781
2018 FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland organoids. Journal of cell science 43 29361536
2021 Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair. Oncogene 42 34127812
2014 Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations. Blood 42 24408322
2014 FGF2 is a target and a trigger of epigenetic mechanisms associated with differences in emotionality: partnership with H3K9me3. Proceedings of the National Academy of Sciences of the United States of America 42 25071177
2021 ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY. Cell death & disease 41 34839358
2013 Identification and characterization of FGF2-dependent mRNA: microRNA networks during lens fiber cell differentiation. G3 (Bethesda, Md.) 41 24142921
2013 Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells. Journal of dental research 40 24186558
2015 Biphasic effects of FGF2 on adipogenesis. PloS one 39 25790378
2003 Expression of CD137 and its ligand in human neurons, astrocytes, and microglia: modulation by FGF-2. Journal of neuroscience research 39 13130507
2017 Fibroblast growth factor 2 (FGF2) regulates cytoglobin expression and activation of human hepatic stellate cells via JNK signaling. The Journal of biological chemistry 38 28916723
2015 Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2. Journal of dental research 38 26276371
2007 FGF2 in asthmatic airway-smooth-muscle-cell hyperplasia. Trends in molecular medicine 37 18055262
2014 Malondialdehyde mediates oxidized LDL-induced coronary toxicity through the Akt-FGF2 pathway via DNA methylation. Journal of biomedical science 36 24490960
2008 Expression analysis of VEGFA, FGF2, TGFbeta1, EGF and IGF1 in human nasal polyposis. Oncology reports 36 18202785
2020 Regulation of mRNA export through API5 and nuclear FGF2 interaction. Nucleic acids research 35 32383752
2018 Single event visualization of unconventional secretion of FGF2. The Journal of cell biology 34 30470711
2014 Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling. Pigment cell & melanoma research 34 24725364
2012 HoxA10 protein regulates transcription of gene encoding fibroblast growth factor 2 (FGF2) in myeloid cells. The Journal of biological chemistry 34 22493287
2019 Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling. Molecular systems biology 33 31777174
2018 FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis and lung cancer. Oncology letters 32 30013642
2022 Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2. Frontiers in immunology 31 36189305
2021 Multiple Therapeutic Applications of RBM-007, an Anti-FGF2 Aptamer. Cells 31 34203430
2016 FGF2 Prevents Sunitinib-Induced Cardiotoxicity in Zebrafish and Cardiomyoblast H9c2 Cells. Cardiovascular toxicology 31 25701259
2001 FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma. International journal of cancer 31 11745459
2014 FGF2 activates TRPC and Ca(2+) signaling leading to satellite cell activation. Frontiers in physiology 30 24575047
1997 Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy. Kidney international 30 8995747
2020 FGF2: a novel druggable target for glioblastoma? Expert opinion on therapeutic targets 28 32174197
2018 FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression. Journal of cellular physiology 28 29215722
2019 Effects of FGF2/FGFR1 Pathway on Expression of A1 Astrocytes After Infrasound Exposure. Frontiers in neuroscience 27 31130839
2010 Signaling pathways implicated in PGF2alpha effects on Fgf2+/+ and Fgf2-/- osteoblasts. Journal of cellular physiology 27 20432442
2009 FGF2 stimulates SDF-1 expression through the Erm transcription factor in Sertoli cells. Journal of cellular physiology 27 19301256
2013 Up-regulated cten by FGF2 contributes to FGF2-mediated cell migration. Molecular carcinogenesis 26 23625726
2010 Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis. Cardiovascular research 26 20817637
2020 The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway. Journal of neurochemistry 25 32936929
2017 Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) synergistically promote steroidogenesis and survival of cultured buffalo granulosa cells. Animal reproduction science 25 28238531
2008 Relative role of upstream regulators of Akt, ERK and CREB in NCAM- and FGF2-mediated signalling. Neurochemistry international 25 18656513
2018 Ablation of low-molecular-weight FGF2 isoform accelerates murine osteoarthritis while loss of high-molecular-weight FGF2 isoforms offers protection. Journal of cellular physiology 24 30144364
2013 PKCε activation promotes FGF-2 exocytosis and induces endothelial cell proliferation and sprouting. Journal of molecular and cellular cardiology 24 23880610
2019 Effect of Testosterone on FGF2, MRF4, and Myostatin in Hypogonadotropic Hypogonadism: Relevance to Muscle Growth. The Journal of clinical endocrinology and metabolism 22 30629183
2018 The FGF2 aptamer inhibits the growth of FGF2-FGFR pathway driven lung cancer cells. Biochemical and biophysical research communications 22 30005872
2006 Modulation of antigenic phenotype in cultured human osteoblast-like cells by FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma. Bioscience reports 22 17029006
2004 Coexpression and regulation of the FGF-2 and FGF antisense genes in leukemic cells. Leukemia research 22 15725477
2000 Diazepam induces FGF-2 mRNA in the hippocampus and striatum. Brain research bulletin 22 11113582
2022 The neuroprotective mechanism of sevoflurane in rats with traumatic brain injury via FGF2. Journal of neuroinflammation 21 35177106
2021 Effect of fibronectin, FGF-2, and BMP4 in the stemness maintenance of BMSCs and the metabolic and proteomic cues involved. Stem cell research & therapy 21 33676544
2020 TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness. PloS one 21 33206726
2016 Stage-specific roles of FGF2 signaling in human neural development. Stem cell research 21 27608170
2015 Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult. Scientific reports 21 26635098
2009 Analytical approaches to uptake and release of hydrogel-associated FGF-2. Journal of materials science. Materials in medicine 21 19851836
2021 FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis. Molecular metabolism 20 34710640
2020 NEAT1 Knockdown Inhibits Keloid Fibroblast Progression by miR-196b-5p/FGF2 Axis. The Journal of surgical research 20 33162101
2018 FGF2 Enhances Odontoblast Differentiation by αSMA+ Progenitors In Vivo. Journal of dental research 20 29649366
2010 Influence of FGF2 and PEG hydrogel matrix properties on hMSC viability and spreading. Journal of biomedical materials research. Part A 20 19768790
2004 Validation of molecular docking calculations involving FGF-1 and FGF-2. Journal of medicinal chemistry 20 15027859