An Epidermis-Permeable Dipeptide Is a Potential Cosmetic Ingredient with Partial Agonist/Antagonist Activity Toward Fibroblast Growth Factor Receptors

The study investigated the potential of a dipeptide, prolyl-isoleucine (Pro-Ile), as a cosmetic ingredient due to its ability to penetrate the epidermis and its partial agonist/antagonist activity toward fibroblast growth factor receptors (FGFRs). Pro-Ile was found to stimulate human keratinocyte growth and activate FGFR3c and FGFR4, with a lesser effect on FGFR1c, showing receptor specificity similar to FGF18. The activity of Pro-Ile was enhanced by heparin and inhibited by an FGFR inhibitor, PD173074. It also modulated the activity of FGF18, enhancing it at low concentrations and suppressing it at higher concentrations. These findings suggested that Pro-Ile could be a useful topical cosmetic ingredient for regulating skin physiology, promoting hair growth, and aiding in wound healing.