Melanin is synthesized by melanocytes in skin epidermis and plays a vital protective role against the ultraviolet radiation of the solar light. UV-exposed keratinocytes secrete α-MSH, which then activates cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling and subsequently upregulates the expression of microphthalmia-associated transcription factor (MITF), the master regulator of melanogenesis, through phosphorylation and activation of the cAMP response element binding protein (CREB) transcription factor. On the other hand, canonical Wnt/β-catenin is activated by Wnt family of secreted glycolipoproteins and causes stabilization of β-catenin by inhibiting GSK-3β through the Wnt signalosome. Upregulated MITF and stabilized β-catenin are translocated into nucleus and bind the target genes for melanogenic enzymes including tyrosinase, tyrosinase related protein-1 (TYRP1), and tyrosinase related protein-2 (TYRP2). In present study, we investigated the effects of MITF and SFRP5 antagonist peptides on melanogenesis and its underling mechanism in vitro and in vivo. Treatment of melanocytes with the MITF and SFRP5 antagonist peptides inhibited α-MSH-induced melanin production and TYR activity. Furthermore, the MITF and SFRP5 antagonist peptides reduced expression of the melanogenic enzyme genes at both mRNA and protein levels in a dose-dependent manner. Moreover, MITF and SFRP5 antagonist peptides decreased the formation of MITF/CREB and MITF/β-catenin complexes, which led to a decrease in melanin synthesis. Collectively, these results suggest that MITF and SFRP5 antagonist peptides might be promising candidates for the treatment of melanogenesis-associated disorders.
Keywords: Peptide, Melanogenesis, MITF, Wnt, Tyrosinase, SFRP5