Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

• Published in: Cellular physiology and biochemistry Vol. 42; no. 6; pp. 2207 - 2219
• Main Authors: Yuan, Jinxia, Chen, Hongtao, Ge, Dawei, Xu, Yu, Xu, Haihua, Yang, Yang, Gu, Ming, Zhou, Yuhe, Zhu, Jingdong, Ge, Ting, Chen, Qun, Gao, Yue, Wang, Yanqing, Li, Xiaowei, Zhao, Yanfang
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2017; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Animals; Antagomirs - metabolism; Cardiac fibrosis; Cell Survival - drug effects; Cells, Cultured; Disease Models, Animal; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Gene expression; Heart attacks; Heart failure; Male; Mice; Mice, Inbred C57BL; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Mir-21; Mortality; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardium - cytology; Myocardium - metabolism; Original Paper; Ostomy; Rats; Rats, Sprague-Dawley; RNA Interference; Rodents; Roles; Signal Transduction - drug effects; Smad7; Smad7 Protein - antagonists & inhibitors; Smad7 Protein - genetics; Smad7 Protein - metabolism; Surgery; TGF-β1; Traditional Chinese medicine; Transforming Growth Factor beta1 - pharmacology; Up-Regulation - drug effects; United States > US; China; Myocardial infarction; Cardiac fibrosis; TGF-β1; Smad7; Mir-21
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000479995

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. Methods: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-β1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice. Results: MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-β1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-β1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice. Conclusion: These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-β/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.