SFRP5 Inhibits The Melanin Synthesis Of Melanocytes Via Regulating Wnt/?-catenin Signaling Pathway In Vitiligo

Objectives: Secreted frizzled-related protein 5(SFRP5)is known to play a pivotal role in regulating the development of many tissues and organs,but its effect on vitiligo is still obscure.This study aims to explore the effect of SFRP5 on melanin synthesis in melanocytes,clarify its specific mechanism,and further explore its role in the development of vitiligo.Methods: We initially detected the expression of SFRP5 in vitiligo tissues and vitiligo melanocytes by immunohistochemistry,qRT-PCR and Western blot analysis.Then,normal epidermal melanocytes(PIG1)were infected with recombinant SFRP5 adenovirus(AdSFRP5),and vitiligo melanocytes(PIG3V)were infected with recombinant siSFRP5 adenovirus(AdsiSFRP5),the tyrosinase(TYR)activity and melanin content were measured.The melanin synthesis and melanogenesis-associated proteins were analyzed by immunocytochemical staining,transmission electron microscopy,scanning electron microscope,qRT-PCR and Western blot.Moreover,Western blot and immunocyto-chemistry experiments were used to detect the effect of SFRP5 on Wnt/?-catenin in melanocytes.Finally,the underlying mechanism and the reversion of SKL2001 on the melanogenesis inhibited by SFRP5 were investigated via Western blot.Results: We first found that SFRP5 is overexpressed in the skinlesions of vitiligo patients.Compared with PIG1 cells,the expression of SFRP5 is increased in PIG3 V cells.SFRP5 inhibits melanin synthesis through MITF and its target proteins downregulation via Wnt/?-catenin signaling.Besides,this inhibitory effect can be reversed by ?-catenin agonist SKL2001.Conclusions: Overall,we demonstrated that SFRP5 could inhibit melanogenesis of melanocytes via Wnt/?-catenin signaling pathway,which could be a prospective therapeutic target for vitiligo.