时间: 15:00-17:00 on Thu., Feb. 17, 2022
题目: Multimodality Regulation of Metabolism and Aging by MG53
MG53, also named TRIM72, is specifically enriched in skeletal muscle and the heart. We and others have previously reported that MG53 participates in muscle membrane repair and cardiac ischemic preconditioning and postconditioning. Recently, we have shown that MG53 also acts as an E3 ligase targeting AMPKa as well as insulin receptor and its interacting protein insulin receptor substrate 1 for ubiquitin-dependent degradation, resulting in impairments of glucose metabolism and the sequelae of metabolic syndrome, including type-2 diabetes (T2D) and various cardiovascular complications. Furthermore, we have demonstrated that MG53 can be secreted as a myokine which binds to and allosterically blocks insulin receptor, contributing to the pathogenesis of systemic insulin resistance in multiple organs. Taken together, our findings indicate that MG53 acts as a multimodal regulator: protecting multiple organs from acute ischemia/reperfusion injury and oxidative stress; whereas when chronically elevated, inducing insulin resistance, metabolic disorders, and accelerated aging. These studies pave the way for MG53 signaling pathway(s)-biased therapies to treat age-related diseases including ischemic heart diseases and a variety of cardiometabolic diseases.
Dr. Rui-Ping Xiao is a Chair Professor and the Dean of the College of Future Technology at Peking University. Dr. Xiao’s research has been focused on cardiometabolic disease, with a major emphasis on a translational approach to take bench discoveries into clinically relevant situations. Ongoing research directions include signaling pathways involved in metabolic syndrome, diabetes and its cardiovascular complications. Currently, Dr. Xiao serves as a Council Member of the International Society of Heart Research and an Associate Editor of the New England Journal of Medicine and an Editorial Board Member for multiple international top journals.