机构：[1]Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China[2]Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China[3]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming, China内科科室皮肤科昆明医科大学附属第一医院[4]Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing, China
Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UVinduced skin cell damages via activating mTOR-Nrf2 signaling.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81673066, 81473684]; Natural Science Foundation of Fujian ProvinceNatural Science Foundation of Fujian Province [2013J01297, 2016J01534]; Joint Funds for the innovation of science and Technology of Fujian province [2016Y91020018]; Outstanding Young Scientist Project of Fujian Province [2015B028, 2016-ZQN-47]
