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 μM, respectively. On the other hand, IC50 of this peptide on binding of FGF‐5 to the FGFR‐1(IIIc)/Fc chimera was 483 μM. 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. J. Cell. Physiol. 197: 272–283, 2003.