Fibroblast growth factor

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Contents

Function

Fibroblast growth factors (FGF) are involved in angiogenesis, wound-healing and embryonic development. FGF is heparin-binding protein. FGF require heparan sulfate (HS) to activate the four FGF cell-surface receptors (FGFR). In vertebrates there are 23 members in the FGF family[1].

  • FGF1 is called acidic FGF.
  • FGF2 is called basic FGF.
  • FGF4 has multiple roles during vertebrate embryogenesis[2].
  • FGF7 is called keratinocyte growth factor which is present in the epitheliazation-phase of wound healing when keratinocytes are covering the wound[3]. FGF7 is aparacrine growth factor in the breast[4].
  • FGF8 has multiple roles in the regulation of embryogenesis, cell differentiation, proliferation and migration. It is required for normal development of normal brain, eye, ear and limb[5].
  • FGF9 is produced and secreted by the prostatic stromal cells[6].
  • FGF10 has essential role in the growth of fetal prostate [7].
  • FGF12 is a key regulator of the vascular smooth muscle cell phenotype switch[8].
  • FGF13 regulates proliferation and differentiation of the skeletal muscle cells [9].
  • FGF18 has al role in organ development and damage repair [10].
  • FGF19 has high affinity to FGFR4[11].
  • FGF21 has a role in regulating body weight in a dietary carbohydrate-dependent manner [12].
  • FGF23 is produced by bone cells and regulates renal phosphate and vitamin D metabolism [13].

See also Fibroblast growth factor receptor and Growth factors.

Disease

Mutations in FGF20 are associated with Parkinson's disease[14].

Relevance

FGF signaling is important in the pathogenesis of a variety of tumor types[15], angiogenesis[16] and wound healing[17]. FGF1 is a potentially safw candidate for restoring euglycaemia without causing a=overt adverse effects[18]. Overexpression of the high molecular weight isoform of FGF2 in bone results in catabolic activity in joint cartilage and bone that leads to osteoarthropathy[19]. FGF12 could be a therapeutic target for treating restenosis and atherosclerosis. FGF18 is overexpressed in ovarian cancer and hence may serve as therapeutic target[20]. FGF19 is overexpressed in lung squamous cell carcinoma and hence may serve as therapeutic target[21].

Structural insights

The heparin binds in the dimer interface of the rat fibroblast growth factor 1[22]. Water molecules are shown as red spheres.

3D structures of fibroblast growth factor

Fibroblast growth factor 3D structures


Rat fibroblast growth factor 1 complex with heparan sulfate (PDB code 2uus)

Drag the structure with the mouse to rotate

References

  1. ↑ Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol. 2001;2(3):REVIEWS3005. Epub 2001 Mar 9. PMID:11276432
  2. ↑ Kosaka N, Sakamoto H, Terada M, Ochiya T. Pleiotropic function of FGF-4: its role in development and stem cells. Dev Dyn. 2009 Feb;238(2):265-76. doi: 10.1002/dvdy.21699. PMID:18792115 doi:http://dx.doi.org/10.1002/dvdy.21699
  3. ↑ Han DS, Li F, Holt L, Connolly K, Hubert M, Miceli R, Okoye Z, Santiago G, Windle K, Wong E, Sartor RB. Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats. Am J Physiol Gastrointest Liver Physiol. 2000 Nov;279(5):G1011-22. doi:, 10.1152/ajpgi.2000.279.5.G1011. PMID:11052999 doi:http://dx.doi.org/10.1152/ajpgi.2000.279.5.G1011
  4. ↑ Palmieri C, Roberts-Clark D, Assadi-Sabet A, Coope RC, O'Hare M, Sunters A, Hanby A, Slade MJ, Gomm JJ, Lam EW, Coombes RC. Fibroblast growth factor 7, secreted by breast fibroblasts, is an interleukin-1beta-induced paracrine growth factor for human breast cells. J Endocrinol. 2003 Apr;177(1):65-81. PMID:12697038
  5. ↑ Liu SB, Ma Z, Sun WL, Sun XW, Hong Y, Ma L, Qin C, Stratton HJ, Liu Q, Jiang JT. The role of androgen-induced growth factor (FGF8) on genital tubercle development in a hypospadiac male rat model of prenatal exposure to di-n-butyl phthalate. Toxicology. 2012 Mar 11;293(1-3):53-8. doi: 10.1016/j.tox.2011.12.010. Epub 2012 , Jan 17. PMID:22273727 doi:http://dx.doi.org/10.1016/j.tox.2011.12.010
  6. ↑ Giri D, Ropiquet F, Ittmann M. FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells. J Cell Physiol. 1999 Jul;180(1):53-60. doi:, 10.1002/(SICI)1097-4652(199907)180:1<53::AID-JCP6>3.0.CO;2-P. PMID:10362017 doi:<53::AID-JCP6>3.0.CO;2-P http://dx.doi.org/10.1002/(SICI)1097-4652(199907)180:1<53::AID-JCP6>3.0.CO;2-P
  7. ↑ Donjacour AA, Thomson AA, Cunha GR. FGF-10 plays an essential role in the growth of the fetal prostate. Dev Biol. 2003 Sep 1;261(1):39-54. PMID:12941620
  8. ↑ Song SH, Kim K, Jo EK, Kim YW, Kwon JS, Bae SS, Sung JH, Park SG, Kim JT, Suh W. Fibroblast Growth Factor 12 Is a Novel Regulator of Vascular Smooth Muscle Cell Plasticity and Fate. Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1928-36. doi:, 10.1161/ATVBAHA.116.308017. Epub 2016 Jul 28. PMID:27470512 doi:http://dx.doi.org/10.1161/ATVBAHA.116.308017
  9. ↑ Lu H, Shi X, Wu G, Zhu J, Song C, Zhang Q, Yang G. FGF13 regulates proliferation and differentiation of skeletal muscle by down-regulating Spry1. Cell Prolif. 2015 Oct;48(5):550-60. doi: 10.1111/cpr.12200. Epub 2015 Jul 31. PMID:26230950 doi:http://dx.doi.org/10.1111/cpr.12200
  10. ↑ Chen G, An N, Shen J, Chen H, Chen Y, Sun J, Hu Z, Qiu J, Jin C, He S, Mei L, Sui Y, Li W, Chen P, Guan X, Chu M, Wang Y, Jin L, Kim K, Li X, Cong W, Wang X. Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice. Nat Commun. 2023 Mar 4;14(1):1235. PMID:36871047 doi:10.1038/s41467-023-36895-1
  11. ↑ Xie MH, Holcomb I, Deuel B, Dowd P, Huang A, Vagts A, Foster J, Liang J, Brush J, Gu Q, Hillan K, Goddard A, Gurney AL. FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4. Cytokine. 1999 Oct;11(10):729-35. PMID:10525310 doi:10.1006/cyto.1999.0485
  12. ↑ Le TDV, Fathi P, Watters AB, Ellis BJ, Besing GK, Bozadjieva-Kramer N, Perez MB, Sullivan AI, Rose JP, Baggio LL, Koehler J, Brown JL, Bales MB, Nwaba KG, Campbell JE, Drucker DJ, Potthoff MJ, Seeley RJ, Ayala JE. Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets. Mol Metab. 2023 Jun;72:101718. PMID:37030441 doi:10.1016/j.molmet.2023.101718
  13. ↑ Bar L, Feger M, Fajol A, Klotz LO, Zeng S, Lang F, Hocher B, Foller M. Insulin suppresses the production of fibroblast growth factor 23 (FGF23). Proc Natl Acad Sci U S A. 2018 May 29;115(22):5804-5809. doi:, 10.1073/pnas.1800160115. Epub 2018 May 14. PMID:29760049 doi:http://dx.doi.org/10.1073/pnas.1800160115
  14. ↑ Klempa I, Stelzner F. [Diagnosis, prognosis and surgical treatment of stomach and duodenal ulcers]. Lebensversicher Med. 1975 Sep;27(5):103-7. PMID:2823
  15. ↑ Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780. PMID:20094046 doi:http://dx.doi.org/10.1038/nrc2780
  16. ↑ Friesel RE, Maciag T. Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. FASEB J. 1995 Jul;9(10):919-25. PMID:7542215
  17. ↑ Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33(5):381-94. PMID:12696985
  18. ↑ Gasser E, Moutos CP, Downes M, Evans RM. FGF1 - a new weapon to control type 2 diabetes mellitus. Nat Rev Endocrinol. 2017 Oct;13(10):599-609. doi: 10.1038/nrendo.2017.78. Epub, 2017 Jun 30. PMID:28664920 doi:http://dx.doi.org/10.1038/nrendo.2017.78
  19. ↑ Meo Burt P, Xiao L, Dealy C, Fisher MC, Hurley MM. FGF2 High Molecular Weight Isoforms Contribute to Osteoarthropathy in Male Mice. Endocrinology. 2016 Dec;157(12):4602-4614. doi: 10.1210/en.2016-1548. Epub 2016, Oct 12. PMID:27732085 doi:http://dx.doi.org/10.1210/en.2016-1548
  20. ↑ Wei W, Mok SC, Oliva E, Kim SH, Mohapatra G, Birrer MJ. FGF18 as a prognostic and therapeutic biomarker in ovarian cancer. J Clin Invest. 2013 Oct;123(10):4435-48. doi: 10.1172/JCI70625. Epub 2013 Sep 9. PMID:24018557 doi:http://dx.doi.org/10.1172/JCI70625
  21. ↑ Zhang X, Kong M, Zhang Z, Xu S, Yan F, Wei L, Zhou J. FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas. Thorac Cancer. 2017 Nov;8(6):655-665. doi: 10.1111/1759-7714.12504. Epub 2017 Sep, 14. PMID:28906590 doi:http://dx.doi.org/10.1111/1759-7714.12504
  22. ↑ Kulahin N, Kiselyov V, Kochoyan A, Kristensen O, Kastrup JS, Berezin V, Bock E, Gajhede M. Dimerization effect of sucrose octasulfate on rat FGF1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Jun 1;64(Pt, 6):448-52. Epub 2008 May 16. PMID:18540049 doi:10.1107/S174430910801066X

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