Tao, LichanBei, YihuaChen, PingLei, ZhiyongFu, SiyiZhang, HaifengXu, JiahongChe, LinChen, XiongwenSluijter, Joost PGDas, SaumyaCretoiu, DragosXu, BinZhong, JiuchangXiao, JunjieLi, Xinli2016-11-182016Tao, L., Y. Bei, P. Chen, Z. Lei, S. Fu, H. Zhang, J. Xu, et al. 2016. “Crucial Role of miR-433 in Regulating Cardiac Fibrosis.” Theranostics 6 (12): 2068-2083. doi:10.7150/thno.15007. http://dx.doi.org/10.7150/thno.15007.1838-7640http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408183Dysregulation 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, α-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-β1 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.en-UScardiac fibrosismiR-433AZIN1JNK1.Journal Article2016-11-1810.7150/thno.15007