PMID- 27698941 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20210623 IS - 1838-7640 (Electronic) IS - 1838-7640 (Linking) VI - 6 IP - 12 DP - 2016 TI - Crucial Role of miR-433 in Regulating Cardiac Fibrosis. PG - 2068-2083 AB - Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, alpha-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-beta1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis. FAU - Tao, Lichan AU - Tao L AD - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Bei, Yihua AU - Bei Y AD - Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China. FAU - Chen, Ping AU - Chen P AD - Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China. FAU - Lei, Zhiyong AU - Lei Z AD - Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht 3508GA, The Netherlands. FAU - Fu, Siyi AU - Fu S AD - Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China. FAU - Zhang, Haifeng AU - Zhang H AD - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Xu, Jiahong AU - Xu J AD - Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. FAU - Che, Lin AU - Che L AD - Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. FAU - Chen, Xiongwen AU - Chen X AD - Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA. FAU - Sluijter, Joost Pg AU - Sluijter JP AD - Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht 3508GA, The Netherlands. FAU - Das, Saumya AU - Das S AD - Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02215, USA. FAU - Cretoiu, Dragos AU - Cretoiu D AD - Victor Babes National Institute of Pathology, Bucharest 050096, Romania.; Division of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania. FAU - Xu, Bin AU - Xu B AD - Innovative Drug Research Center of Shanghai University, Shanghai 200444, China. FAU - Zhong, Jiuchang AU - Zhong J AD - State Key Laboratory of Medical Genomics & Shanghai Institute of Hypertension, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. FAU - Xiao, Junjie AU - Xiao J AD - Cardiac Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China. FAU - Li, Xinli AU - Li X AD - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. LA - eng GR - R01 HL122547/HL/NHLBI NIH HHS/United States GR - UH3 TR000901/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160910 PL - Australia TA - Theranostics JT - Theranostics JID - 101552395 RN - 0 (MicroRNAs) RN - 0 (Mirn433 microRNA, mouse) SB - IM CIN - Theranostics. 2017 Jun 1;7(8):2287-2288. PMID: 28740551 EIN - Theranostics. 2021 Jun 8;11(15):7618-7619. PMID: 34158871 MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Fibrosis/*pathology MH - Gene Expression Profiling MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - Myoblasts/physiology MH - Myocardial Infarction/*complications/*pathology MH - Rats PMC - PMC5039681 OTO - NOTNLM OT - AZIN1 OT - JNK1. OT - cardiac fibrosis OT - miR-433 COIS- The authors declare no competing financial interests. EDAT- 2016/10/05 06:00 MHDA- 2017/10/17 06:00 PMCR- 2016/01/01 CRDT- 2016/10/05 06:00 PHST- 2016/01/18 00:00 [received] PHST- 2016/08/06 00:00 [accepted] PHST- 2016/10/05 06:00 [entrez] PHST- 2016/10/05 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - thnov06p2068 [pii] AID - 10.7150/thno.15007 [doi] PST - epublish SO - Theranostics. 2016 Sep 10;6(12):2068-2083. doi: 10.7150/thno.15007. eCollection 2016.