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MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4.
Huang, Ying; Qi, Yuan; Du, Jian-Qing; Zhang, Dai-fu.
Afiliación
  • Huang Y; Pu Dong New Area People's Hospital, Department of Cardiology , Huan-Nan Road 490#, Shanghai, 201200 , China +86 021 50331692 ; +86 021 50331692 ; daifu_zhang001@163.com.
Expert Opin Ther Targets ; 18(12): 1355-65, 2014 Dec.
Article en En | MEDLINE | ID: mdl-25322725
ABSTRACT

BACKGROUND:

Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis.

METHODS:

The myocardial infarction (MI) mice model was induced and cardiac fibroblasts were cultured. Histological analyses, quantitative real-time polymerase chain reaction and Western blotting analysis were used.

RESULTS:

We found that the miR-34 cluster, especially miR-34a, was upregulated in the MI heart. In vivo, inhibition of miR-34a reduces the severity of experimental cardiac fibrosis in mice. TGF-ß1 increased miR-34a expression in cardiac fibroblasts. Overexpressing miR-34a levels increased the profibrogenic activity of TGF-ß1 in cardiac fibroblast, whereas inhibition miR-34a levels weakened the activity. Finally, we showed that miR-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of Smad4 expression.

CONCLUSIONS:

Our findings provide evidence that miR-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting Smad4, which suggests that miR-34a may be new marker for cardiac fibrosis progression and that inhibition of miR-34a may be a promising strategy in the treatment of cardiac fibrosis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: MicroARNs / Proteína Smad4 / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Expert Opin Ther Targets Asunto de la revista: TERAPEUTICA Año: 2014 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: MicroARNs / Proteína Smad4 / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Expert Opin Ther Targets Asunto de la revista: TERAPEUTICA Año: 2014 Tipo del documento: Article