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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00249

MiR-144-3p enhances cardiac fibrosis after myocardial infarction by targeting PTEN

 Xiaolong Yuan1*, Jinchun Pan2, Lijuan Wen1, Baoyong Gong2,  Jiaqi Li1, Hongbin Gao2, Weijiang Tan2, Shi Liang2,  Hao Zhang1 and Xilong Wang2
  • 1South China Agricultural University, China
  • 2Guangdong Laboratory Animals Monitoring Institute, China

Myocardial infarction (MI) may cause heart failure and seriously harm human health. During the genesis of cardiac fibrosis after MI, the proliferation and migration of cardiac fibroblasts contribute to secretion and maintenance of extracellular matrix (ECM) components. Many miRNAs have been highly implicated in the processes of cardiac fibrosis after MI. However, the molecular mechanisms for how miRNAs involve in cardiac fibrosis remain largely unexplored. Based on MI model in miniature pigs, the potential miRNAs involved in MI were identified by using small RNA sequencing. Using human cardiac fibroblasts as a cellular model, EdU, Transwell, and the expression of ECM-related proteins were applied to investigate the cell proliferation, migration and collagen synthesis. In this study, using MI model based on miniature pigs, 84 miRNAs were identified as the differentially expressed miRNAs between MI and control group, and miR-144-3p, one of differentially expressed miRNAs, was identified to be higher expressed in infarct area. The cell proliferation, migration activity, and the mRNA and protein levels of the ECM-related genes were significantly increased by miR-144-3p mimic but significantly decreased by miR-144-3p inhibitor in cardiac fibroblasts. Furthermore, miR-144-3p was observed to repress transcription and translation of PTEN, and interfering with the expression of PTEN upregulated the mRNAs and proteins levels of α-SMA, Col1A1, and Col3A1, and promoted the proliferation and migration of cardiac fibroblasts, which was in line with that of miR-144-3p mimics, but this observation could be reversed by miR-144-3p inhibitor. Collectively, miR-144-3p promotes cell proliferation, migration, and collagen production by targeting PTEN in cardiac fibroblasts, suggesting that miR-144-3p-mediated-PTEN regulation might be a novel therapeutic target for cardiac fibrosis after MI.

Keywords: miR-144-3p, Pten, cardiac fibrosis, Myocardial Infarction, Extracellular Matrix

Received: 18 Jul 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Yuan, Pan, Wen, Gong, Li, Gao, Tan, Liang, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Xiaolong Yuan, South China Agricultural University, Guangzhou, China, yxl@scau.edu.cn