RGD Reference Report - Crucial Role of miR-433 in Regulating Cardiac Fibrosis. - Rat Genome Database

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Crucial Role of miR-433 in Regulating Cardiac Fibrosis.

Authors: Tao, Lichan  Bei, Yihua  Chen, Ping  Lei, Zhiyong  Fu, Siyi  Zhang, Haifeng  Xu, Jiahong  Che, Lin  Chen, Xiongwen  Sluijter, Joost Pg  Das, Saumya  Cretoiu, Dragos  Xu, Bin  Zhong, Jiuchang  Xiao, Junjie  Li, Xinli 
Citation: Tao L, etal., Theranostics. 2016 Sep 10;6(12):2068-2083. doi: 10.7150/thno.15007. eCollection 2016.
RGD ID: 14700802
Pubmed: (View Article at PubMed) PMID:27698941
DOI: Full-text: DOI:10.7150/thno.15007

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.

Annotation

Disease Annotations    
Cardiac Fibrosis  (IEP,IMP,ISO)
cardiomyopathy  (IEP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Mir433  (microRNA 433)

Genes (Mus musculus)
Mir433  (microRNA 433)

Genes (Homo sapiens)
MIR433  (microRNA 433)


Additional Information