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METTL3, a component of methyltransferase complex, participates in multiple biological processes associated with mammalian development and disease progression. However, the role of METTL3 in cardiac fibrosis is still unknown. We performed fibroblasts activation with TGF\u2010\u03b21 (20\u00a0ng\/mL) in vitro and established in vivo mouse models with lentivirus to assess the effects of METTL3 on cardiac fibroblasts proliferation and collagen formation. Methylated RNA immunoprecipitation (MeRIP) was used to define the potential fibrosis\u2010regulated gene. The expression level of METTL3 was increased in cardiac fibrotic tissue of mice with chronic myocardial infarction and cultured cardiac fibroblats (CFs) treated with TGF\u2010\u03b21. Enforced expression of METTL3 promoted proliferation and fibroblast\u2010to\u2010myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite. Silence of METTL3 by lentivirus carrying METTL3 siRNA markedly alleviated cardiac fibrosis in MI mice. Transcriptome and N6\u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) profiling analyses revealed that the expression and m\n                    <jats:sup>6<\/jats:sup>\n                    A level of collagen\u2010related genes were altered after silence of METTL3. METTL3\u2010mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A modification is critical for the development of cardiac fibrosis, providing a molecular target for manipulating fibrosis and the associated cardiac diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.201903169r","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T04:30:54Z","timestamp":1604550654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts"],"prefix":"10.1096","volume":"35","author":[{"given":"Tingting","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"key laboratory of Myocardial Ischemia Ministry of Education Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education) College of Pharmacy Harbin Medical University Harbin P.R. China"},{"name":"Northern Translational Medicine Research and Cooperation Center Heilongjiang Academy of Medical Sciences Harbin Medical University Harbin P.R. 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