FGF5

Receptor

FGF5 is a 268 amino acid, 29.1 kDa protein, which also naturally occurs as a 123 amino acid isoform splice variant (FGF5s). 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. The receptor for FGF5, FGFR1, is largely expressed in the dermal papilla cells of the hair follicle. The alternatively spliced isoform FGF5s, has been identified as an antagonist of FGF5 in a number of studies.

Role in hair cycling

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. 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.

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, dogs, mice, rabbits, donkeys, sheep and goats, 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.

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.

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. 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.

Blocking FGF5 in the human scalp extends the hair cycle, resulting in less hair fall, faster hair growth rate and increased hair growth. 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, and single molecule members of the monoterpenoid family 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.

References

References

1. (2015). "The Fibroblast Growth Factor signaling pathway". Wiley Interdisciplinary Reviews: Developmental Biology.
2. (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.
3. (March 2000). "Dual-mode regulation of hair growth cycle by two Fgf-5 gene products". The Journal of Investigative Dermatology.
4. (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.
5. (January 2002). "Fibroblast growth factor 5 inhibits hair growth by blocking dermal papilla cell activation". Biochemical and Biophysical Research Communications.
6. (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.
7. (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.
8. (September 1994). "FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations". Cell.
9. (June 2007). "Mutations within the FGF5 gene are associated with hair length in cats". Animal Genetics.
10. (2007). "Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats". The Journal of Heredity.
11. (August 2013). "Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs". Animal Genetics.
12. (August 2006). "The long and the short of it: evidence that FGF5 is a major determinant of canine 'hair'-itability". Animal Genetics.
13. (July 2008). "[Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits]". Yi Chuan = Hereditas.
14. (September 2014). "Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys". Genetics, Selection, Evolution.
15. (February 2009). "[Effects of FGF5 gene on fibre traits on Inner Mongolian cashmere goats]". Yi Chuan = Hereditas.
16. (2016). "Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers". PLOS ONE.
17. (February 2013). "Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans". BMC Evolutionary Biology.
18. (March 2017). "Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness". Nature Communications.
19. (2007). "Sanguisorba Officinalis Root Extract Has FGF-5 Inhibitory Activity and Reduces Hair Loss by Causing Prolongation of the Anagen Period". Nishinihon J. Dermatology.
20. (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.