A novel role of erythropoietin in skin pigmentation through melanin production

Abstract

Melanin protects the skin from UV radiation and oxidative stress. Its synthesis in melanocytes is regulated by alpha-MSH and the Melanocortin 1 Receptor signaling pathway. The erythropoietin receptor (EPOR) is expressed in melanocytes; however, its function is unknown. EPOR is a receptor for erythropoietin (EPO), which promotes hematopoiesis and protection from hypoxic stress. We hypothesized that EPOR is involved in pigment regulation. Mouse skin tissue models, cultured melanocytes, and human-derived artificial skin models were treated with recombinant human EPO (rhEPO) and/or EPO-derived peptides, and examined changes in pigmentation and cell signaling pathways. rhEPO significantly increased pigmentation, induced ERK and AKT phosphorylation, and increased tyrosinase expression in mouse melanocytes. Some EPO-derived peptides increased pigmentation in an artificial human skin model. Our results indicate that EPOR activation acts as a regulator of melanin synthesis and suggest that EPOR agonists have potential for the treatment of pigment-related diseases as well as cosmetic applications.