Nature：MG53蛋白为治疗心血管病提供药物靶点

　　最新出版的《自然》杂志发表了博雅干细胞集团首席科学家、北京大学分子医学研究所教授肖瑞平与团队所作的关于MG53（一种E3泛素连接酶）调节动物模型心血管功能和新陈代谢新功效的研究成果。

　　研究人员发现该蛋白不仅直接与心血管的修复相关，更重要的是通过抑制该基因还可有效控制糖尿病和代谢综合征的发生。

　　该研究是全球生物医药领域近5年来在心血管疾病和代谢综合征领域的又一发现。

　　心血管疾病和肥胖症疾病已严重影响人类的生命健康。据世界心脏联盟统计，全世界范围内每死亡3人中，就有1人的死因是心血管疾病。心血管疾病的死亡率高于癌症、艾滋病等其他疾病，在中国城市老年居民中心血管病患病率高达62%。MG53蛋白的发现为治疗心血管疾病提供了重要的药物靶点。

Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders

Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes1. Although skeletal muscle accounts for 70–90% of insulin-stimulated glucose disposal2, 3, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.