Senescent Fibroblast-Derived GDF15 Induces Skin Pigmentation

Abstract

Senescent fibroblasts play a role in aging pigmentation. In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were cocultured with fibroblasts infected with the GDF15 lentivirus or GDF15 short hairpin RNA. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via beta-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. These results suggest that senescent fibroblast-derived GDF15 stimulates skin pigmentation and may play a role in aging-associated pigmentation.