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MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension.

Authors: Castoldi, G  Di Gioia, CR  Bombardi, C  Catalucci, D  Corradi, B  Gualazzi, MG  Leopizzi, M  Mancini, M  Zerbini, G  Condorelli, G  Stella, A 
Citation: Castoldi G, etal., J Cell Physiol. 2012 Feb;227(2):850-6. doi: 10.1002/jcp.22939.
Pubmed: (View Article at PubMed) PMID:21769867
DOI: Full-text: DOI:10.1002/jcp.22939

MicroRNAs play an important role in myocardial diseases. MiR-133a regulates cardiac hypertrophy, while miR-29b is involved in cardiac fibrosis. The aim of this study was to evaluate whether miR-133a and miR-29b play a role in myocardial fibrosis caused by Angiotensin II (Ang II)-dependent hypertension. Sprague-Dawley rats were treated for 4 weeks with Ang II (200 ng/kg/min) or Ang II + irbesartan (50 mg/kg/day in drinking water), or saline by osmotic minipumps. At the end of the experimental period, cardiac miR-133a and miR-29b expression was measured by real-time PCR, and myocardial fibrosis was evaluated by morphometric analysis. A computer-based prediction algorithm led to the identification of collagen 1a1 (Col1A1) as a putative target of miR-133a. A reporter plasmid bearing the 3'-untranslated regions (UTRs) of Col1A1 mRNA was constructed and luciferase assay was performed. MiR-133a suppressed the activity of luciferase when the reporter gene was linked to a 3'-UTR segment of Col1A1 (P < 0.01). Mutation of miR-133a binding sites in the 3'-UTR of Col1A1 mRNA abolished miR-133a-mediated repression of reporter gene activity, showing that Col1A1 is a real target of miR-133a. In vivo, Ang II caused an increase in systolic blood pressure (P < 0.0001, tail cuff) and myocardial fibrosis in presence of a decrease in miR-133a (P < 0.01) and miR-29b (P < 0.01), and an increase in Col1A1 expression (P < 0.01). These effects were abolished by Ang II administration + irbesartan. These data demonstrate a relationship between miR-133a and Col1A1, suggesting that myocardial fibrosis occurring in Ang II-dependent hypertension is regulated by the down-regulation of miR-133a and miR-29b through the modulation of Col1A1 expression.

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CRRD Object Information
CRRD ID: 5688337
Created: 2012-02-28
Species: All species
Last Modified: 2012-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.