Home General Physiology and Biophysics 2023 General Physiology and Biophysics Vol.42, No.5, p. 417–429, 2023

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Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

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General Physiology and Biophysics Vol.42, No.5, p. 417–429, 2023

Title: DNMT1‑induced miR‑133b suppression via methylation promotes myocardial fibrosis after myocardial infarction
Author: Songlin Zhang, Hang Xie, Yajuan Du, Boxiang Wang, Beidi Lan, Haiyan Wang

Abstract: Myocardial fibrosis is an underlying cause of many cardiovascular diseases. Novel insights into the epigenetic control of myocardial fibrosis are now emerging. The current work is focused on investigating the biological role of DNA methyltransferase 1 (DNMT1) in myocardial fibrosis as well as the underlying mechanism. Our findings revealed that DNMT1 expression levels were upregulated, whereas miR-133b expression levels were decreased in a rat model of myocardial fibrosis following myocardial infarction. In vitro, the expression levels of DNMT1 increased and those of miR-133b decreased after Ang-II treatment in cardiac fibroblasts. DNMT1 knockdown inhibited Ang‐II-induced cardiac myofibroblast activation, and DNMT1 overexpression increased the proliferation and collagen generation of cardiac myofibroblasts. Furthermore, DNMT1 expression levels decreased, while miR-133b expression levels increased after treatment with 5-Aza (5-Azacytidine, a known inhibitor of DNA methylation) in Ang-II-induced cardiac fibroblasts. BSP (Bisulfite sequencing PCR) results showed a marked decrease in methylation levels in the miR-133b promoter region upon overexpression of DNMT1, whereas knockdown of DNMT1 blocked increased methylation levels in the miR-133b promoter region in Ang-II-induced cardiac fibroblasts. Finally, 5-Aza treatment reduced the progression of myocardial fibrosis after myocardial infarction in rats in vivo. Collectively, our results suggest that DNMT1 mediates CTGF expression in cardiac fibroblast activation by regulating the methylation of miR-133b. The present work reveals the unique role of the DNMT1/miR-133b/CTGF axis in myocardial fibrosis, thus suggesting its great therapeutic potential in the treatment of cardiac diseases.

Keywords: DNMT1— miR-133b — Methylation — Myocardial fibrosis
Published online: 19-Sep-2023
Year: 2023, Volume: 42, Issue: 5 Page From: 417, Page To: 429

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