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miR-145-5p targets paxillin to attenuate angiotensin II-induced pathological cardiac hypertrophy via downregulation of Rac 1, pJNK,p-c-Jun,NFATc3, ANP and by Sirt-1 upregulation |
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| Authors: | Lin Kuan-Ho Kumar V Bharath Shanmugam Tamilselvi Shibu Marthandam Asokan Chen Ray-Jade Kuo Chia-Hua Ho Tsung-Jung Padma V Vijaya Yeh Yu-Lan Huang Chih-Yang |
| Institution: | 1.Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan ;2.College of Medicine, China Medical University, Taichung, Taiwan ;3.Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan ;4.Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan ;5.Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan ;6.Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan ;7.Chinese Medicine, Hualien Tzu Chi Hospital, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan ;8.Department of Biotechnology, Bharathiar University, Coimbatore, 641046, India ;9.Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan ;10.Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Taipei, 11260, Taiwan ;11.Center of General Education, Tzu Chi University of Science and Technology, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan ;12.Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan ;13.Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan ; |
| Abstract: | Pathological cardiac hypertrophy is associated with many diseases including hypertension. Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-145-5p in the cardiac setting is still unclear. In this study, H9C2 cells were overexpressed with microRNA-145-5p, and then treated with Ang-II for 24 h, to study the effect of miR-145-5p on Ang-II-induced myocardial hypertrophy in vitro. Results showed that Ang-II treatment down-regulated miR-145-5p expression were revered after miR-145-5p overexpression. Based on results of bioinformatics algorithms, paxillin was predicted as a candidate target gene of miR-145-5p, luciferase activity assay revealed that the luciferase activity of cells was substantial downregulated the following co-transfection with wild paxillin 3′UTR and miR-145-5p compared to that in scramble control, while the inhibitory effect of miR-145-5p was abolished after transfection of mutant paxillin 3′UTR. Additionally, overexpression of miR-145-5p markedly inhibited activation of Rac-1/ JNK /c-jun/ NFATc3 and ANP expression and induced SIRT1 expression in Ang-II treated H9c2 cells. Jointly, our study suggested that miR-145-5p inhibited cardiac hypertrophy by targeting paxillin and through modulating Rac-1/ JNK /c-jun/ NFATc3/ ANP / Sirt1 signaling, therefore proving novel downstream molecular pathway of miR-145-5p in cardiac hypertrophy |
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