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Fibroblast growth factor

Revision as of 14:00, 19 March 2019 by Alexander Berchansky (talk | contribs)

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].
  • FGF23 is produced by bone cells and regulates renal phosphate and vitamin D metabolism [10].

Disease

Mutations in FGF20 are associated with Parkinson's disease[11].

Relevance

FGF signaling is important in the pathogenesis of a variety of tumor types[12], angiogenesis[13] and wound healing[14]. FGF1 is a potentially safw candidate for restoring euglycaemia without causing a=overt adverse effects[15]. Overexpression of the high molecular weight isoform of FGF2 in bone results in catabolic activity in joint cartilage and bone that leads to osteoarthropathy[16]. FGF12 could be a therapeutic target for treating restenosis and atherosclerosis. FGF18 is overexpressed in ovarian cancer and hence may serve as therapeutic target[17]. FGF19 is overexpressed in lung squamous cell carcinoma and hence may serve as therapeutic target[18].

Structural insights

[19]. Water molecules are shown as red spheres.

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

Drag the structure with the mouse to rotate

3D structures of fibroblast growth factor3D structures of fibroblast growth factor

Updated on 19-March-2019

ReferencesReferences

  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. ↑ 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
  11. ↑ Klempa I, Stelzner F. [Diagnosis, prognosis and surgical treatment of stomach and duodenal ulcers]. Lebensversicher Med. 1975 Sep;27(5):103-7. PMID:2823
  12. ↑ 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
  13. ↑ Friesel RE, Maciag T. Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. FASEB J. 1995 Jul;9(10):919-25. PMID:7542215
  14. ↑ 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
  15. ↑ 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
  16. ↑ 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
  17. ↑ 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
  18. ↑ 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
  19. ↑ 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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