Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts
| Autor: | Xin Zhou, Wanqi Yang, Yilin Xie, Wendi Shang, Yang Zhou, Xue Dong, Tingting Li, Jiaxu Wu, Zhenwei Pan, Yanjie Lu, Mingyu Zhang, Ying Li, Wenmei Jiang, Yuting Zhuang, Shuang Su |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cardiac fibrosis Myocardial Infarction Transfection Biochemistry Transforming Growth Factor beta1 Extracellular matrix Transcriptome Mice 03 medical and health sciences 0302 clinical medicine In vivo Fibrosis Genetics medicine Animals Gene silencing Gene Silencing Myocardial infarction Myofibroblasts Molecular Biology Cells Cultured Cell Proliferation business.industry Methyltransferase complex Myocardium Methyltransferases medicine.disease Up-Regulation Mice Inbred C57BL Disease Models Animal 030104 developmental biology Cancer research Collagen business 030217 neurology & neurosurgery Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 35 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Cardiac fibrosis is characterized by the activation of cardiac fibroblasts and accumulation of extracellular matrix. 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-β1 (20 ng/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-regulated 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-β1. Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast 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-methyladenosine (m6 A) profiling analyses revealed that the expression and m6 A level of collagen-related genes were altered after silence of METTL3. METTL3-mediated m6 A modification is critical for the development of cardiac fibrosis, providing a molecular target for manipulating fibrosis and the associated cardiac diseases. |
| Databáze: | OpenAIRE |
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