high-resolution micrograph of a fibroblast labeled with fluorescent dyes

What is FGF?

FGF, also known as fibroblast growth factor, represents a family of approximately two dozen heparin-binding proteins that play pivotal roles in numerous cellular processes related to development and repair of tissues including brain, skin, and lungs.

FGFs function by binding to and activating high-affinity FGF receptors (FGFR) on target cells, causing a signal transduction cascade involving kinases and transcription factors. Activation of signaling pathways by fibroblast growth factors results in cellular effects such as mitogenesis, differentiation, migration, angiogenesis, and wound healing.

Explore FGF signaling pathways

Biochemical properties of fibroblast growth factors

FGFs are medium sized single-chain proteins with molecular weights ranging from 15–25 kDa possessing a conserved core of about 120 amino acids. Originally two biochemical classes of fibroblast growth factor, acidic (FGF-1) and basic (FGF-2) were identified based on their isoelectric points (pI); now seven subfamilies are recognized based on sequence homology.

Applications of FGFs in biomedical research

Recombinant proteins from the FGF family are used in numerous cell culture applications. FGFs are important for maintaining, expanding and differentiating diverse types of cells in culture. FGF recombinant proteins are also employed to determine signaling interactions and pathways. For example:

  • FGF-basic: maintenance of pluripotent stem cells
  • FGF-10: differentiation of human pluripotent stem cells to insulin-producing pancreatic-like cells
  • FGF-7/KGF: expansion of neural stem and progenitor cells
  • FGF-6: study of pathways involved in muscle development

Functions of fibroblast growth factors

Proteins in the FGF family share the functional abilities to signal through at least one of four tyrosine kinase receptors (FGFR1 through FGFR4) and interact with heparin sulphate proteoglycans (HSPGs).

FGF function varies depending on the type of receptor engaged as well as target cell location and phenotype. The chart below lists the known receptors, target cells, and functions of each member of the FGF family.

FGF name/typeTarget cells (partial list)FGF receptor(s)FGF function(s) (partial list)
FGF1 (Acidic FGF) Heparin-Binding Growth Factor-1 (HBGF-1) ECGF-beta (Endothelial Cell Growth Factor-beta)mesenchymal, neuroectodermal endothelial cellsall FGF receptorsAngiogenic in vivo, mitogenic in in vitro, wound healing
FGF2 (Basic FGF) Heparin-Binding Growth Factor-2 (HBGF-2) Prostatropinmesenchymal, neuroectodermal endothelial cells1b, 1c, 2c, 3c, 4Vasculogenesis, wound healing, angiogenesis, hematopoiesis, neuron survival
FGF3 int-2epithelial cells that express FGF receptor 2b2bMesoderm induction, angiogenesis, inner ear development
FGF4 Heparin Secretory Transforming protein (HST-1) Transforming protein KS3 Heparin-Binding Growth Factor-4 (HBGF-4)cells that express FGF receptors1c, 2c, 3c, 4Angiogenesis, vertebrate limb development and development of stomach cancer
FGF5 Heparin-Binding Growth Factor-5 (HBGF-5) Smag-82cells that express FGF receptors1c, 2cHair growth and development
FGF6 Heparin-Binding Growth Factor-6 (HBGF-6) HST-2cells that express FGF receptors1c, 2c, 4Skeletal muscle development
FGF7/KGF (Keratinocyte Growth Factor) HST-6 Heparin-Binding Growth Factor-7 (HBGF-7)keratinocytes and epithelial cells that express FGF receptor 2b2bKeratinocyte growth factor, kidney and lung development, angiogenesis and wound healing
FGF8 Androgen-Induced Growth Factor (AIGF)Heparin-Binding Growth Factor-8 (HBGF-8)mammary carcinoma cells and other cells that express FGF receptors2c, 3c, 4 (possibly 1c)Limb, central nervous system, cardiac outflow tract development
FGF9 Glia Activating Factor (GAF)Heparin-Binding Growth Factor-9 (HBGF-9)glial cells, astrocyte cells and other cells that express FGF receptors1c, 2c, 3b, 3c, 4Glia-activating factor, motor neuron survival, lung and testes development
A Keratinocyte growth factor-2epithelial cells that express FGF receptor 2b2bWound healing, multi-organ including limb and lung development
FGF11 FGFB Fibroblast growth Factor Homologous Factor-3(FHF-3)unknown to dateunknown to dateAppears to be involved in nervous system development and function
FGF12 FGFC Fibroblast growth factor Homologous Factor-1(FHF-1)NIH3T3 fibroblast cell line1, 2, 3, 4Appears to be involved in nervous system development and function
FGF13 FGFD Fibroblast growth Factor Homologous Factor-2(FHF-2)unknown to dateunknown to dateAppears to be involved in nervous system development and function
FGF14 FGFE Fibroblast growth factor Homologous Factor-4(FHF-4)unknown to dateunknown to dateRegulates central nervous system development and function
FGF15 FGFF, identified in mouse not humancells that express FGF receptor 44Regulator of cell division and patterning in specific regions of embryonic brain, spinal cord and sensory organs
FGF16 FGFGcells that express FGF receptors2c, 3cCentral nervous system development
FGF17 FGFHcells that express FGF receptors1c, 2c, 3c, 4Signals induction and patterning of embryonic brain
FGF18 zFGF5 FGFIcells that express FGF receptors1c, 2c, 3c, 4An essential regulator of long bone and calvarial development
FGF19 FGFJ, identified in human onlycells that express FGF receptor 44Expressed during brain development and during embryogenesis, regulates multiple metabolic processes in adulthood
FGF20 FGFKepithelial and mesenchymal cells1c, 2c, 3cExpressed during limb and brain development
FGF21 FGFLneurons, beta cells1cExpressed in liver, brain, skeletal muscle; may play a role in metabolic disease
FGF22 FGFMhair follicle, skin, keratinocytes, neurons2bMay be involved in cutaneous development and repair, and brain development
FGF23 FGFNrenal proximal epithelial cells3cExpressed in brain and thymus, regulates phosphate homeostasis, mutant in hypophosphatemic rickets, regulates multiple metabolic processes in adulthood
References
  1. Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov 8(3):235–253. 
  2. Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2(3):REVIEWS3005. 
  3. Sochacka M, Opalinski L, Szymczyk J, et al. (2020) FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner. Cell Commun Signal 18(1):69. 
  4. Yun YR, Won JE, Jeon E, et al. (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142. 
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