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

The study identified a dipeptide, prolyl-isoleucine (Pro-Ile), as a potential cosmetic ingredient due to its ability to penetrate the epidermis and partially mimic fibroblast growth factor (FGF) activity. Pro-Ile stimulated human keratinocyte growth and activated FGFR3c and FGFR4, with a lesser effect on FGFR1c, showing receptor specificity similar to FGF18. Its activity was enhanced by heparin and inhibited by an FGFR inhibitor. Pro-Ile 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 used topically to regulate skin physiology, hair growth, and wound healing.