Decapeptide with fibroblast growth factor (FGF)‐5 partial sequence inhibits hair growth suppressing activity of FGF‐5

Abstract

Earlier studies demonstrated that knock-out of fibroblast growth factor-5 gene (Fgf-5) prolonged anagen VI phase of hair cycle, resulting long hairs in the mice. We showed the activities on hair growth of the two Fgf-5 gene products, one of which, FGF-5 suppressed hair growth by inhibiting anagen proceeding and inducing the transition from anagen to catagen, and FGF-5S, a shorter polypeptide with FGF-5-antagonizing activity translated from alternatively spliced mRNA, suppressed this activity of FGF-5. As the results suggested that FGF-5 antagonist would increase hair growth, we synthesized various peptides having partial sequences of human FGF-5 and FGF-5S and determined their FGF-5 antagonist activity. Among them, a decapeptide designated P3 (95-VGIGFHLQIY-104) that aligns with receptor binding sites of FGF-1 and FGF-2 suppressed FGF-5-induced proliferation of BALB/3T3 A31 and NIH/3T3 murine fibroblasts, and FGF receptor-1c (FGFR-1c)-transfected Ba/F3 cell line (FR-Ba/F3 cells). IC50s of this peptide on these cell proliferations were 64, 28, 146 microM, respectively. On the other hand, IC50 of this peptide on binding of FGF-5 to the FGFR-1(IIIc)/Fc chimera was 483 microM. Examination in dorsal depilated mice revealed that the P3 peptide reduced the activity of FGF-5 to recover hair pigmentation and hair follicle lengths. The classification of histologically observed skin sections showed FGF-5-induced delations of anagen procedure had reduced by the P3 peptide. The anti-Ki67 antibody staining of hair follicles was inhibited by administration of FGF-5, and this inhibition by FGF-5 was recovered by administration of the P3 peptide. The P3 peptide alone did not affect hair follicle length and hair cell proliferation. These results indicate that the decapeptide antagonized FGF-5 activity in vivo, and reduced the inhibition of FGF-5 in hair growth, confirming that FGF-5 inhibitors are promising substances against hair loss and/or for promoting hair growth.

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

“…We first assessed the ability of test compounds to inhibit FGF5-induced proliferation of the engineered FGF receptor 1-expressing BaF3 cell line 27. The BaF3 cell line used in the study is a cell line engineered to express FGFR1c, originally used to study the splice variant of FGF5 known as FGF5s 26. The BaF3 cell lineage is IL-3 dependent and responds to the presence of IL-3 by proliferating.…”

“…Alternate mRNA splicing of FGF5 results in the translation of long (FGF5) and short (FGF5S) isoforms, which are known to act in concert. FGF5S acts as an antagonist to the catagen-inducing effect of FGF5,25 and in this vein there is potential for exogenous inhibitors of FGF5 to promote hair growth, as demonstrated by Ito et al26…”

In search of the “hair cycle clock”: a guided tour

“…To list only a few well-studied examples from the murine system, WNT-b-catenin-Lef 1 signalling, noggin, and STAT3 drive telogen follicles into anagen, and Shh, HGF, and FGF7 (KGF) further promote this process (Ellis et al, 2003;Oro and Higgins, 2003;Van Mater et al, 2003;Celso et al, 2004). BMP4 and 17-bestradiol arrest the follicle in telogen Guha et al, 2004); IGF-1, HGF, GDNF, and VEGF prolong the duration of anagen (Su et al, 1999;Lindner et al, 2000;Mecklenburg et al, 2000), while FGF5, TGFb1, TGFb2, the neurotrophins NT-3, NT-4, and BDNF, as well as p75NTR signalling, induce catagen (Botchkarev et al, 1998b(Botchkarev et al, , 2004Soma et al, 1998Soma et al, , 2002Foitzik et al, 2000;Ito et al, 2003) (Fig. 5).…”

Efficacy of Postbiotics in a PRP-Like Cosmetic Product for the Treatment of Alopecia Area Celsi: A Randomized Double-Blinded Parallel-Group Study

“…Such peptides possess a higher stability and specificity, are less expensive than PRP and can be easily included in a topical formulation. These benefits have been shown in many applications, ranging from skin rejuvenation [37,38] to wound-healing [38] and hair growth [39][40][41][42][43][44].…”