{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:33:50Z","timestamp":1789220030936,"version":"build-2803163510"},"reference-count":32,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:p>Cardiometabolic diseases, including diabetes and its cardiovascular complications, are the global leading causes of death, highlighting a major unmet medical need. Over the past decade, mitsugumin 53 (MG53), also called TRIM72, has emerged as a powerful agent for myocardial membrane repair and cardioprotection, but its therapeutic value is complicated by its E3 ligase activity, which mediates metabolic disorders. Here, we show that an E3 ligase\u2013dead mutant, MG53-C14A, retains its cardioprotective function without causing metabolic adverse effects. When administered in normal animals, both the recombinant human wild-type MG53 protein (rhMG53-WT) and its E3 ligase\u2013dead mutant (rhMG53-C14A) protected the heart equally from myocardial infarction and ischemia\/reperfusion (I\/R) injury. However, in diabetic db\/db mice, rhMG53-WT treatment markedly aggravated hyperglycemia, cardiac I\/R injury, and mortality, whereas acute and chronic treatment with rhMG53-C14A still effectively ameliorated I\/R-induced myocardial injury and mortality or diabetic cardiomyopathy, respectively, without metabolic adverse effects. Furthermore, knock-in of MG53-C14A protected the mice from high-fat diet\u2013induced metabolic disorders and cardiac damage. Thus, the E3 ligase\u2013dead mutant MG53-C14A not only protects the heart from acute myocardial injury but also counteracts metabolic stress, providing a potentially important therapy for the treatment of acute myocardial injury in metabolic disorders, including diabetes and obesity.<\/jats:p>","DOI":"10.2337\/db21-0322","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T13:50:16Z","timestamp":1638193816000},"page":"298-314","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":21,"title":["MG53 E3 Ligase\u2013Dead Mutant Protects Diabetic Hearts From Acute Ischemic\/Reperfusion Injury and Ameliorates Diet-Induced Cardiometabolic Damage"],"prefix":"10.2337","volume":"71","author":[{"given":"Han","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Robeson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Han","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Kun","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyun","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxiang","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"},{"name":"Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-467X","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"},{"name":"Key Laboratory of Molecular Cardiovascular Sciences, Institute of Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Ping","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China"},{"name":"Beijing City Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China"},{"name":"Peking University\u2013Nanjing Joint Institute of Translational Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"2022031309594915000_B1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41591-020-0786-7","article-title":"Improving prevention strategies for cardiometabolic 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