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Study on overexpression of methyltransferase-like 3 promoting myocardial fibrosis
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1.Guangdong Cardiovascular Institute & Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China;2.Shantou University Medical College, Shantou, Guangdong 515041, China;3.School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China;4.The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280, China)

Clc Number:

R363

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    Abstract:

    Aim To investigate the effect of overexpression of methyltransferase-like 3 (METTL3) on myocardial fibrosis. Methods METTL3 protein expression was detected in the myocardium of patients with heart failure (HF) and the healthy donors by Western blot assay. A C57BL/6 mouse model of transverse aortic constriction (TAC) surgery-induced myocardial fibrosis was established, and METTL3 protein expression was detected in the myocardium of TAC mice and sham mice. A cell model of angiotensinⅡ(AngⅡ)-induced myocardial fibrosis in mouse cardiac fibroblasts (CF) was established and used to detect METTL3 expression by Western blot assay. Expression of fibrosis-related genes, including collagen type Ⅰα1 (COL1α1), collagen type Ⅲ α1 (COL3α1) and actin α2 (ACTα2), was detected in mouse CF with adenovirus-mediated overexpression of METTL3. Flow cytometry, EdU and Transwell migration assay were used to detect proliferation and migration activity of mouse CF, respectively. Effects of cardiac specific expression of METTL3 on cardiac function and fibrosis were explored in mice subjected to TAC surgery. Results Protein expression of METTL3 was significantly increased in the myocardium of HF patients (P＜0.05). Consistently, significant up-regulation of METTL3 was observed in the myocardium of TAC mice and AngⅡ-treated mouse CF (P＜0.05, respectively). Overexpression of METTL3 could markedly enhance mouse CF proliferation and migration activities, as well as expression of fibrosis-related genes in mouse CF. Compared with mice in the sham group, significant increase of fibrosis-related gene expression, cardiac fibrosis and cardiac function injury were observed in TAC-induced mice with cardiac specific overexpression of METTL3. Conclusion Overexpression of METTL3 promotes cardiac fibrosis in mice.

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LIU Yanjun, WEI Peijian, HUANG Zhiqi, GUO Jishen, CHEN Zerun, ZHU Jiening, XU Jindong, SHAN Zhixin, GUO Huiming. Study on overexpression of methyltransferase-like 3 promoting myocardial fibrosis[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2022,30(6):476-482.

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History
  • Received:October 09,2021
  • Revised:December 25,2021
  • Online: May 10,2022
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