Fibroblast Growth Factor Family (FGF)

Fibroblast Growth Factors (FGFs) are potent regulators of cell proliferation, differentiation and function and are critically important in normal development, tissue maintenance, wound repair and angiogenesis. FGFs are also linked with several pathological conditions. Mutations in FGF genes are associated with various diseases such as cancer, cardiovascular disease, osteoarthritis, diabetes, Parkinson’s disease and hypophosphatemia2.

Human FGF family contain 22 members, designated FGF-1 through FGF-23 (except FGF-15). All FGFs except four members (FGF11, FGF12, FGF13 and FGF14) bind to FGF Receptors.and are classified into six different FGF sub-families3. Members of the FGF family generally share 30-50% amino acid sequence homology, have two conserved cysteine residues, and bind with high affinity to heparin.

The FGF ligands elicit their action through four transmembrane tyrosine kinase receptors – FGFR1, FGFR2, FGFR3, and FGFR4. Activated FGFRs transduce signals through RAS/MAP kinase pathway, PI3 kinase/AKT pathway and PLCγ pathway. Although FGF was originally named after its fibroblast mitogenicity4, some FGFs do not induce fibroblast growth at all.

Acidic FGF (aFGF) and basic FGF (bFGF) are the prototypic FGF members named because of their different isoelectric points5. Acidic FGF has high expression levels in brain, retina, bone matrix and osteosarcomas.Basic FGF is found in a variety of tissues, including pituitary gland, neural tissue, adrenal cortex, corpus luteum, and placenta.

Acidic and basic FGFs stimulate proliferation of cells of mesodermal origin, and many cells of neuroectodermal, ectodermal, and endodermal origin. They are chemotactic and mitogenic for endothelial cells and induce the release of agents that break down basement membranes. These two FGFs along with other members in FGF family play significant roles in modulating cell proliferation, migration, differentiation and angiogenesis2 (table 2).

Table 1: Functions of FGFs based on existing studies2

Ligands Cell Proliferation Cell Migration Cell Differentiation Angiogenesis
FGF1  
FGF2
FGF4    
FGF7  
FGF8      
FGF10      
FGF18      
FGF20      

Immortalized cortical cell line in the presence of fibroblast growth factors

Immortalized cortical cell line in the presence of growth factors bFGF (Cat. No. F0291) and EGF (Cat. No. E9644). Cultures are predominantly GFAP staining astrocytes (red) with a few β III-tubulin staining neurons (green). Counterstaining of cell nuclei with Hoechst dye. Images of human neural stem cells courtesy of ReNeuron Limited, United Kingdom.

Materials

     

Adapted from:  BioFiles 2009, 4.5, 11 by Jennifer Fries

 

References

  1. Ornitz, D. M., and Itoh, N. (2015) The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip. Rev. Dev. Biol. 4, 215–266.
  2. Yun, Y.-R., Won, J. E., Jeon, E., Lee, S., Kang, W., Jo, H., Jang, J.-H., Shin, U. S., and Kim, H.-W. (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J. Tissue Eng. 2010, 218142.
  3. Itoh, N. (2007) The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. Biol. Pharm. Bull. 30, 1819–1825.
  4. (4) Gospodarowicz, D., Ferrara, N., Schweigerer, L., and Neufeld, G. (1987) Structural characterization and biological functions of fibroblast growth factor. Endocr. Rev. 8, 95–114.
  5. (5) DePhillips, P., and Lenhoff, A. M. (2004) Relative retention of the fibroblast growth factors FGF-1 and FGF-2 on strong cation-exchange sorbents. J. Chromatogr. A 1036, 51–60.

 

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