distinct pigmentary and melanocortin 1 receptor–dependent components of cutaneous defense against ultraviolet radiation不同的色素和肾上腺皮质receptor-dependent皮肤防御紫外线辐射的组成部分.pdfVIP

Distinct Pigmentary and Melanocortin 1 Receptor–Dependent Components of Cutaneous Defense against Ultraviolet Radiation Craig S. April1,2, Gregory S. Barsh1,2* 1 Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America, 2 Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America Genetic variation at the melanocortin 1 receptor (MC1R) is an important risk factor for developing ultraviolet (UV) radiation–induced skin cancer, the most common form of cancer in humans. The underlying mechanisms by which the MC1R defends against UV-induced skin cancer are not known. We used neonatal mouse skin (which, like human skin, contains a mixture of melanocytes and keratinocytes) to study how pigment cells and Mc1r genotype affect the W-v W-v genome-level response to UV radiation. Animals without viable melanocytes (Kit /Kit ) or animals lacking a e e functional Mc1r (Mc1r /Mc1r ) were exposed to sunburn-level doses of UVB radiation, and the patterns of large-scale gene expression in the basal epidermis were compared to each other and to nonmutant animals. Our analysis revealed discrete Kit- and Mc1r-dependent UVB transcriptional responses in the basal epidermis. The Kit-dependent UVB response was characterized largely by an enrichment of oxidative and endoplasmic reticulum stress genes, highlighting a distinctive role for pigmented melanocytes in mediating antioxidant defenses against genotoxic stresses within the basal epidermal environment. By contrast, the Mc1r-depend