Decapeptide with fibroblast growth factor (FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF-5.
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.
D016475:3T3 Cells; D000595:Amino Acid Sequence / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
C496450:Fgf5 protein, mouse; D019394:Ki-67 Antigen; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors