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Osteopontin (OPN) is a secreted glycophosphoprotin that has been shown to play an important role in cardiac fibrosis and remodeling. Here our objective was to determine whether microRNA181a would regulate OPN expression and cardiac fibrosis in mice.
cardiac fibroblast cells isolated from adult mouse hearts were cultured and treated with microRNA181a mimics and inhibitor, and the expression of OPN and collagen I were examined by quantitative RT-PCR and protein analysis, respectively. Cardiac fibrosis was induced by Angiotensis-II infusion for 4 weeks via osmotic mini-pumps. MicroRNA181a agomir and negative control were injected via mouse tail vein, and cardiac fibrosis was assessed via optical microscopic imaging analysis. Cardiac expression of OPN and extracellular matrix proteins were assessed by quantitative RT-PCR.
The expression of OPN and collagen I were significantly decreased in cultured cardiac fibroblast cells treated with microRNA181a mimics, whereas increased when the cells were treated with microRNA181a inhibitor. The mice injected with microRNA181a agomir exhibited less cardiac fibrosis when compared with those injected with negative control. Consistently, Injection of microRNA181a agomir also decreased the expression levels of OPN and collagen in vivo.
Our data demonstrated that microRNA181a regulates OPN expression in vitro and in vivo, and increased microRNA181a expression could reduce cardiac fibrosis.