Crucial Role of miR-433 in Regulating Cardiac Fibrosis.

Abstract

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, 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.

• Authors: Lichan Tao, Yihua Bei, Ping Chen, Zhiyong Lei, Siyi Fu, Haifeng Zhang, Jiahong Xu, Lin Che, Xiongwen Chen, Joost Pg Sluijter, Saumya Das, Dragos Cretoiu, Bin Xu, Jiuchang Zhong, Junjie Xiao, Xinli Li
• Journal: Theranostics (Theranostics) Vol. 6 Issue 12 Pg. 2068-2083 ( 2016) ISSN: 1838-7640 [Electronic] Australia
• PMID: 27698941 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• Mirn433 microRNA, mouse

Topics

• Animals
• Cell Differentiation
• Cells, Cultured
• Fibrosis (pathology)
• Gene Expression Profiling
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Myoblasts (physiology)
• Myocardial Infarction (complications, pathology)
• Rats