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M6A methylation plays a role in fibrosis development. However, its underlying mechanism remains poorly understood. This study explores the role and molecular mechanisms of m6A methylation in regulating cardiac fibrosis after myocardial infarction (MI). A mouse myocardial fibrosis model post\u2010MI was established by ligating the left coronary artery. Corresponding gene knockdown was achieved in\u00a0vitro or in\u00a0vivo using short hairpin RNA or fibroblast\u2010specific AAV9 virus. Echocardiography assessed cardiac function in mice, while Masson staining determined the degree of collagen deposition post\u2010MI. The meRIP\u2010Seq kit detected mRNA methylation levels in myocardial tissue and hypoxia\u2010treated cardiac fibroblasts. Expression of RNA methylation\u2010related enzymes, fibrosis\u2010related proteins, and SMOC2 expression in the myocardial tissue or cardiac fibroblasts were detected using western blotting. Actinomycin D assessed SMOC2 mRNA stability. Results demonstrated increased levels of m6A methylation and METTL3 expression in myocardial fibrosis tissue post\u2010MI and in hypoxia\u2010treated cardiac fibroblasts. In\u00a0vivo METTL3 downregulation reduced the fibrotic area and improved cardiac function, while METTL3 downregulation in\u00a0vitro can alleviate cardiac fibroblast proliferation and differentiation after hypoxia. Mechanistically, METTL3 promoted SMOC2 mRNA stability by increasing its m6A methylation level, thereby regulating cardiac fibroblast proliferation and differentiation. Together, our work uncovers a critical link between METTL3 and SMOC2, providing insight into the functional importance of the mRNA m6A methylation and its modulators in cardiac fibrosis post MI.<\/jats:p>","DOI":"10.1111\/jcmm.70829","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T04:12:27Z","timestamp":1757131947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>METTL3<\/scp>\n                    Silencing Suppresses Cardiac Fibrosis Post Myocardial Infarction via\n                    <scp>m6A<\/scp>\n                    Modification of\n                    <scp>SMOC2<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"given":"Yanru","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Affiliated to Southeast University  Nanjing 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