{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:56:33Z","timestamp":1789160193773,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["91639104"],"award-info":[{"award-number":["91639104"]}]},{"name":"Major Research Plan of the National Natural Science Foundation of China","award":["81800348"],"award-info":[{"award-number":["81800348"]}]},{"name":"Nation Natural Science Foundation of China","award":["91639104"],"award-info":[{"award-number":["91639104"]}]},{"name":"Nation Natural Science Foundation of China","award":["81800348"],"award-info":[{"award-number":["81800348"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site \u201cA\u201d to \u201cT\u201d, and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI.<\/jats:p>","DOI":"10.3390\/genes14030591","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:52:21Z","timestamp":1677469941000},"page":"591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1360-6290","authenticated-orcid":false,"given":"Hao","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linnan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqiang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41392-020-00411-4","article-title":"Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis","volume":"6","author":"Xu","year":"2021","journal-title":"Signal Transduct. 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