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 (200ng/kg/min) or Ang II+irbesartan (50mg/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

Castoldi, G., Di Gioia, C., Bombardi, C., Catalucci, D., Corradi, B., Gualazzi, M., et al. (2012). MiR-133a regulates collagen 1A1: Potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension. JOURNAL OF CELLULAR PHYSIOLOGY, 227(2), 850-856 [10.1002/jcp.22939].

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

CASTOLDI, GIOVANNA;STELLA, ANDREA
2012

Abstract

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 (200ng/kg/min) or Ang II+irbesartan (50mg/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
Articolo in rivista - Articolo scientifico
Scientifica
angiotensin II, myocardial fibrosis, mir-133a, animal models, collagen 1a1
English
Castoldi, G., Di Gioia, C., Bombardi, C., Catalucci, D., Corradi, B., Gualazzi, M., et al. (2012). MiR-133a regulates collagen 1A1: Potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension. JOURNAL OF CELLULAR PHYSIOLOGY, 227(2), 850-856 [10.1002/jcp.22939].
Castoldi, G; Di Gioia, C; Bombardi, C; Catalucci, D; Corradi, B; Gualazzi, M; Leopizzi, M; Mancini, M; Zerbini, G; Condorelli, G; Stella, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/27106
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