FGF5

Last updated
FGF5
Identifiers
Aliases FGF5 , HBGF-5, Smag-82, TCMGLY, fibroblast growth factor 5
External IDs OMIM: 165190 MGI: 95519 HomoloGene: 3283 GeneCards: FGF5
Orthologs
SpeciesHumanMouse
Entrez

2250

14176

Ensembl

ENSG00000138675

ENSMUSG00000029337

UniProt

P12034

P15656

RefSeq (mRNA)

NM_033143
NM_001291812
NM_004464

NM_001277268
NM_010203

RefSeq (protein)

NP_001278741
NP_004455
NP_149134

NP_001264197
NP_034333

Location (UCSC) Chr 4: 80.27 – 80.34 Mb Chr 5: 98.4 – 98.42 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fibroblast growth factor 5 is a protein that in humans is encoded by the FGF5 gene.

Contents

The majority of FGF family members are glycosaminoglycan binding proteins which possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF proteins interact with a family of specific tyrosine kinase receptors, a process often regulated by proteoglycans or extracellular binding protein cofactors. A number of intracellular signalling cascades are known to be activated after FGF-FGFR interaction including PI3K-AKT, PLCγ, RAS-MAPK and STAT pathways. [5]

Receptor

FGF5 is a 268 amino acid, 29.1 kDa protein, which also naturally occurs as a 123 amino acid isoform splice variant (FGF5s). [6] [7] FGF5 is produced in the outer root sheath of the hair follicle as well as perifollicular macrophages, with maximum expression occurring in the late anagen phase of the hair cycle. [8] [9] The receptor for FGF5, FGFR1, is largely expressed in the dermal papilla cells of the hair follicle. [8] [9] The alternatively spliced isoform FGF5s, has been identified as an antagonist of FGF5 in a number of studies. [6] [7] [10]

Role in hair cycling

Research comparing different breeds of dogs has demonstrated FGF5 as a major contributing factor in coat length. Research comparing dogs with different coat lengths has demonstrated FGF5 as a major contributing factor..gif
Research comparing different breeds of dogs has demonstrated FGF5 as a major contributing factor in coat length.

The only described function of FGF5 in adults is in the regulation of the hair cycle. FGF5 performs a critical role in the hair cycle, where it acts as the key signalling molecule in initiating the transition from the anagen (growth) phase to the catagen (regression) phase. [11] [12] Evidence of this activity was initially gathered via targeted disruption of the homolog of the FGF5 gene in mice, which resulted in a phenotype with abnormally long hair. [12]

In numerous genetic studies of long haired phenotypes of animals it has been shown that small changes in the FGF5 gene can disrupt its expression, leading to an increase in the length of the anagen phase of the hair cycle, resulting in phenotypes with extremely long hair. This has been demonstrated in many species, including cats, [13] [14] dogs, [15] [16] mice, [12] rabbits, [17] donkeys, [18] sheep and goats, [19] where it is often referred to as the angora mutation. Recently, CRISPR modification of goats to artificially knock out the FGF5 gene, was shown to result in higher wool yield, without any fertility or other negative effects on the goats. [20]

It has been hypothesised that, in an alternate type of mutation, positive selection for increased expression of the FGF5 protein was one of the contributing factors in the evolutionary loss of hair in cetaceans as they transitioned from the terrestrial to the aquatic environment. [21]

FGF5 also affects the hair cycle in humans. Individuals with mutations in FGF5 exhibit familial trichomegaly, a condition that involves a significant increase in the portion of anagen phase hair as well as extremely long eyelashes. [11] FGF5 has also been identified as a potentially important factor in androgenetic alopecia. In 2017, a large genome wide association study of men with early onset androgenetic alopecia identified polymorphisms in FGF5 as having a strong association with male pattern hair loss. [22]

Blocking FGF5 in the human scalp extends the hair cycle, resulting in less hair fall, faster hair growth rate and increased hair growth. [23] [24] In vitro methods using engineered cell lines and FGFR1 expressing dermal papilla cells have identified a number of naturally derived botanical isolates including Sanguisorba officnalis , [23] and single molecule members of the monoterpenoid family [24] as inhibitors (blockers) of FGF5. Clinical studies have shown that topical application of formulations containing these natural extracts and molecules are beneficial in men and women experiencing hair loss. [23] [24]

Related Research Articles

<span class="mw-page-title-main">Leg hair</span> Hair in the leg areas of adolescent and adult humans

Leg hair is hair that grows on the legs of humans, generally appearing after the onset of puberty. For aesthetic reasons and for some sports, people shave, wax, epilate, or use hair removal creams to remove the hair from their legs: see leg shaving.

<span class="mw-page-title-main">Paracrine signaling</span> Form of localized cell signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

<span class="mw-page-title-main">Basic fibroblast growth factor</span> Growth factor and signaling protein otherwise known as FGF2

Fibroblast growth factor 2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. It binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins, themselves a family of closely related molecules. Fibroblast growth factor protein was first purified in 1975; soon thereafter three variants were isolated: 'basic FGF' (FGF2); Heparin-binding growth factor-2; and Endothelial cell growth factor-2. Gene sequencing revealed that this group is the same FGF2 protein and is a member of a family of FGF proteins.

Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.

<span class="mw-page-title-main">FGF1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 1, (FGF-1) also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the FGF1 gene. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycosylated 17-18 kDa protein. Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins.

<span class="mw-page-title-main">FGF3</span> Protein-coding gene in humans

INT-2 proto-oncogene protein also known as FGF-3 is a protein that in humans is encoded by the FGF3 gene.

<span class="mw-page-title-main">Bone morphogenetic protein 4</span> Human protein and coding gene

Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23.

<span class="mw-page-title-main">Fibroblast growth factor receptor 2</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 is a protein that in humans is encoded by the FGFR2 gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor.

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

<span class="mw-page-title-main">FRS2</span> Protein-coding gene in humans

Fibroblast growth factor receptor substrate 2 is a protein that in humans is encoded by the FRS2 gene.

<span class="mw-page-title-main">FGF7</span> Protein-coding gene in the species Homo sapiens

Keratinocyte growth factor is a protein that in humans is encoded by the FGF7 gene.

<span class="mw-page-title-main">FGF10</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

<span class="mw-page-title-main">Fibroblast growth factor 8</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 8(FGF-8) is a protein that in humans is encoded by the FGF8 gene.

<span class="mw-page-title-main">FGF9</span> Protein-coding gene in the species Homo sapiens

Glia-activating factor is a protein that in humans is encoded by the FGF9 gene.

<span class="mw-page-title-main">FGF4</span> Fibroblast growth factor gene

Fibroblast growth factor 4 is a protein that in humans is encoded by the FGF4 gene.

<span class="mw-page-title-main">FGF18</span> Mammalian protein found in Homo sapiens

Fibroblast growth factor 18 (FGF18) is a protein that is encoded by the Fgf18 gene in humans. The protein was first discovered in 1998, when two newly-identified murine genes Fgf17 and Fgf18 were described and confirmed as being closely related by sequence homology to Fgf8. The three proteins were eventually grouped into the FGF8 subfamily, which contains several of the endocrine FGF superfamily members FGF8, FGF17, and FGF18. Subsequent studies identified FGF18's role in promoting chondrogenesis, and an apparent specific activity for the generation of the hyaline cartilage in articular joints.

<span class="mw-page-title-main">FGF14</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 14 is a biologically active protein that in humans is encoded by the FGF14 gene.

<span class="mw-page-title-main">FGF13</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 13 is a protein that in humans is encoded by the FGF13 gene.

<span class="mw-page-title-main">FGF6</span> Protein-coding gene in humans

Fibroblast growth factor 6 is a protein that in humans is encoded by the FGF6 gene.

Fibroblast growth factor 22 is a protein which in humans is encoded by the FGF22 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000138675 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029337 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Ornitz DM, Itoh N (2015). "The Fibroblast Growth Factor signaling pathway". Wiley Interdisciplinary Reviews: Developmental Biology. 4 (3): 215–66. doi:10.1002/wdev.176. PMC   4393358 . PMID   25772309.
  6. 1 2 Suzuki S, Kato T, Takimoto H, Masui S, Oshima H, Ozawa K, Suzuki S, Imamura T (December 1998). "Localization of rat FGF-5 protein in skin macrophage-like cells and FGF-5S protein in hair follicle: possible involvement of two Fgf-5 gene products in hair growth cycle regulation". The Journal of Investigative Dermatology. 111 (6): 963–72. doi: 10.1046/j.1523-1747.1998.00427.x . PMID   9856803.
  7. 1 2 Suzuki S, Ota Y, Ozawa K, Imamura T (March 2000). "Dual-mode regulation of hair growth cycle by two Fgf-5 gene products". The Journal of Investigative Dermatology. 114 (3): 456–63. doi: 10.1046/j.1523-1747.2000.00912.x . PMID   10692103.
  8. 1 2 Rosenquist TA, Martin GR (April 1996). "Fibroblast growth factor signalling in the hair growth cycle: expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle". Developmental Dynamics. 205 (4): 379–86. doi: 10.1002/(SICI)1097-0177(199604)205:4<379::AID-AJA2>3.0.CO;2-F . PMID   8901049.
  9. 1 2 Ota Y, Saitoh Y, Suzuki S, Ozawa K, Kawano M, Imamura T (January 2002). "Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation". Biochemical and Biophysical Research Communications. 290 (1): 169–76. doi:10.1006/bbrc.2001.6140. PMID   11779149.
  10. ↑ He X, Chao Y, Zhou G, Chen Y (January 2016). "Fibroblast growth factor 5-short (FGF5s) inhibits the activity of FGF5 in primary and secondary hair follicle dermal papilla cells of cashmere goats". Gene. 575 (2 Pt 2): 393–398. doi:10.1016/j.gene.2015.09.034. PMID   26390813.
  11. 1 2 Higgins CA, Petukhova L, Harel S, Ho YY, Drill E, Shapiro L, Wajid M, Christiano AM (July 2014). "FGF5 is a crucial regulator of hair length in humans". Proceedings of the National Academy of Sciences of the United States of America. 111 (29): 10648–53. Bibcode:2014PNAS..11110648H. doi: 10.1073/pnas.1402862111 . PMC   4115575 . PMID   24989505.
  12. 1 2 3 Hébert JM, Rosenquist T, Götz J, Martin GR (September 1994). "FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations". Cell. 78 (6): 1017–25. doi:10.1016/0092-8674(94)90276-3. PMID   7923352. S2CID   44491318.
  13. ↑ Drögemüller C, Rüfenacht S, Wichert B, Leeb T (June 2007). "Mutations within the FGF5 gene are associated with hair length in cats". Animal Genetics. 38 (3): 218–21. doi:10.1111/j.1365-2052.2007.01590.x. PMID   17433015.
  14. ↑ Kehler JS, David VA, Schäffer AA, Bajema K, Eizirik E, Ryugo DK, Hannah SS, O'Brien SJ, Menotti-Raymond M (2007). "Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats". The Journal of Heredity. 98 (6): 555–66. doi:10.1093/jhered/esm072. PMC   3756544 . PMID   17767004.
  15. ↑ Dierks C, Mömke S, Philipp U, Distl O (August 2013). "Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs". Animal Genetics. 44 (4): 425–31. doi:10.1111/age.12010. PMID   23384345.
  16. ↑ Housley DJ, Venta PJ (August 2006). "The long and the short of it: evidence that FGF5 is a major determinant of canine 'hair'-itability". Animal Genetics. 37 (4): 309–15. doi:10.1111/j.1365-2052.2006.01448.x. PMID   16879338.
  17. ↑ Li CX, Jiang MS, Chen SY, Lai SJ (July 2008). "[Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits]". Yi Chuan = Hereditas. 30 (7): 893–9. doi: 10.3724/sp.j.1005.2008.00893 . PMID   18779133.
  18. ↑ Legrand R, Tiret L, Abitbol M (September 2014). "Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys". Genetics, Selection, Evolution. 46 (1): 65. doi:10.1186/s12711-014-0065-5. PMC   4175617 . PMID   25927731.
  19. ↑ Liu HY, Yang GQ, Zhang W, Zhu XP, Jia ZH (February 2009). "[Effects of FGF5 gene on fibre traits on Inner Mongolian cashmere goats]". Yi Chuan = Hereditas. 31 (2): 175–9. doi:10.3724/sp.j.1005.2009.00175. PMID   19273426.
  20. ↑ Wang X, Cai B, Zhou J, Zhu H, Niu Y, Ma B, Yu H, Lei A, Yan H, Shen Q, Shi L, Zhao X, Hua J, Huang X, Qu L, Chen Y (2016). "Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers". PLOS ONE. 11 (10): e0164640. Bibcode:2016PLoSO..1164640W. doi: 10.1371/journal.pone.0164640 . PMC   5068700 . PMID   27755602.
  21. ↑ Chen Z, Wang Z, Xu S, Zhou K, Yang G (February 2013). "Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans". BMC Evolutionary Biology. 13: 34. doi:10.1186/1471-2148-13-34. PMC   3608953 . PMID   23394579.
  22. ↑ Heilmann-Heimbach S, Herold C, Hochfeld LM, Hillmer AM, Nyholt DR, Hecker J, et al. (March 2017). "Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness". Nature Communications. 8: 14694. Bibcode:2017NatCo...814694H. doi:10.1038/ncomms14694. PMC   5344973 . PMID   28272467.
  23. 1 2 3 Maeda T, Yamamoto T, Isikawa Y, et al. (2007). "Sanguisorba Officinalis Root Extract Has FGF-5 Inhibitory Activity and Reduces Hair Loss by Causing Prolongation of the Anagen Period". Nishinihon J. Dermatology. 69 (1): 81–86. doi:10.2336/nishinihonhifu.69.81.
  24. 1 2 3 Burg D, Yamamoto M, Namekata M, Haklani J, Koike K, Halasz M (2017). "Promotion of anagen, increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process". Clinical, Cosmetic and Investigational Dermatology. 10: 71–85. doi:10.2147/CCID.S123401. PMC   5338843 . PMID   28280377.

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