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This study evaluates recombinant human MG53 (rhMG53) and overexpression of MG53 in a mouse SCD model induced by lipopolysaccharide. Outcomes include echocardiographic cardiac performance, survival, inflammation, and cardiomyocyte apoptosis. Mechanistically, MG53 suppresses TLR4 transcriptional activity by ubiquitinating ATF2, reducing TLR4 expression.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mg53-protects-against-septic-cardiac-dysfunction-by-ubiquitinating-atf2-original-manuscript-journal-of-advanced-research/434399/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mg53-protects-against-septic-cardiac-dysfunction-by-ubiquitinating-atf2-original-manuscript-journal-of-advanced-research/434399.png","ImageObject",300,407,{"name":92,"@type":93},"Jordan Avery","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is septic cardiac dysfunction and why is it important in sepsis?","Question",{"text":112,"@type":113},"Septic cardiac dysfunction is a common complication of sepsis and the leading cause of death in septic patients. Mortality is much higher when cardiac dysfunction is present.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study model septic cardiac dysfunction in mice and deliver MG53?",{"text":117,"@type":113},"C57BL/6J mice received intraperitoneal lipopolysaccharide to generate the SCD model. MG53 was overexpressed via intravenously injected adeno-associated virus, and rhMG53 was administered intraperitoneally.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism explains how MG53 protects the heart in septic cardiac dysfunction?",{"text":121,"@type":113},"MG53 inhibits TLR4 transcriptional activity by ubiquitinating ATF2, a transcriptional factor for TLR4, which ultimately lowers TLR4 expression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},434399,1790833564,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Journal of Advanced Research 79 (2026) 263–275  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \nOriginal Manuscript  \nMG53 protects against septic cardiac dysfunction by ubiquitinating ATF2 Miao Tian a,b,c, 1, Yu Shi a,b,c, 1, Xue Gong a,b,c, Wenjie Tan a,b,c, Xinyi Guo a,b,c, Yinghong Chen a,b,c,  \nPeili Yang a,b,c, Hongmei Ren a,b,c, Qi Cai a,b,c, Jianjie Ma d, Chunyu Zeng a,b,c,e,f,g,⁎, Gengze Wu a,b,c,e,⁎  \na Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, PR China  \nb Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, PR China  \nc Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, PR China d Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA  \ne State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, The Third Military Medical University, Chongqing, PR China  \nf Cardiovascular Research Center of Chongqing College, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Chongqing, PR China g Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China  \nh i g h l i g h t s  \n• E3 ubiquitination ligase MG53 is highly expressed in heart and decreased in sepsis.  \n• Recombinant human MG53 significantly improve sepsis-impaired cardiac function and survival rate of mice.  \n• MG53 alleviate inflammation and apoptosis by inhibiting TLR4.  \n• MG53 ubiquitinate transcriptional factor ATF2 via its RING domain.  \n• RhMG53 is promising in the treatment of sepsis.  \ng r a p h i c a l a b s t r a c t  \na r t i c l e i n f o  \nArticle history:  \nReceived 22 December 2024 Revised 16 March 2025  \nAccepted 16 March 2025  \nAvailable online 17 March 2025  \nKeywords:  \nSeptic cardiac dysfunction MG53  \nInflammation Apoptosis TLR4  \nATF2  \na b s t r a c t  \nIntroduction: Septic cardiac dysfunction (SCD) is the most common complication of sepsis, which has become the primary cause of death in intensive care units. The muscle-specific protein mitsugumin-53 (MG53) has been identified to protect cell integrity as a ‘‘Molecular Band-Aid”.  \nObjectives: The recombinant human MG53 (rhMG53) pretreatment has been reported to prevent cardiac function damage caused by cecal ligation and puncture (CLP). However, whether or not MG53 protects against SCD remains to be further clarified.  \nMethods: C57BL/6J mice were intraperitoneally injected with lipopolysaccharide (LPS) to generate the SCD model. MG53 was overexpressed by intravenously injected adeno-associated virus, and therhMG53 was administrated intraperitoneally. The cardiac function was evaluated by echocardiography, and the cardiac inflammation was assessed through ELISA and Western blot. The mechanisms of MG53 were studied by quantitative real-time PCR (qPCR) and co-immunoprecipitation (co-IP) .  \nResults: Our present study found that MG53 expression was lower in hearts from SCD mice than controls. Overexpression or exogenous MG53 treatment alleviated cardiac dysfunction, improved survival rate in SCD mice, accompanied with improved pathological changes, reduced cardiomyocyte apoptosis, and lowered inflammatory factor levels in serum or hearts. Mechanistically, MG53 inhibited TLR4 transcriptional activity by ubiquitinating ATF2, an essential transcriptional factor for TLR4, which ultimately reduced the expression of TLR4.  \n⁎ Corresponding authors at: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, PR China.  \nE-mail addresses: [zengchunyu@tmmu.edu.cn](zengchunyu@tmmu.edu.cn) (C. Zeng), [wugengze@tmmu.edu.cn](wugengze@tmmu.edu.cn) (G. Wu).  \n1 Contribute equally to this work.  \n[https://","cbCailEltv5QgUNS","https://ap.wps.com/l/cbCailEltv5QgUNS","pdf",6209657,13,"English","# Introduction\n# Objectives\n# Methods\n# Results\n# Conclusion","[{\"question\":\"What is septic cardiac dysfunction and why is it important in sepsis?\",\"answer\":\"Septic cardiac dysfunction is a common complication of sepsis and the leading cause of death in septic patients. Mortality is much higher when cardiac dysfunction is present.\"},{\"question\":\"How did the study model septic cardiac dysfunction in mice and deliver MG53?\",\"answer\":\"C57BL/6J mice received intraperitoneal lipopolysaccharide to generate the SCD model. MG53 was overexpressed via intravenously injected adeno-associated virus, and rhMG53 was administered intraperitoneally.\"},{\"question\":\"What mechanism explains how MG53 protects the heart in septic cardiac dysfunction?\",\"answer\":\"MG53 inhibits TLR4 transcriptional activity by ubiquitinating ATF2, a transcriptional factor for TLR4, which ultimately lowers TLR4 expression.\"}]","MG53 protects against septic cardiac dysfunction by ubiquitinating ATF2 - Original Manuscript - Journal of Advanced Research | PDF",1790669078,33]