1. Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy.
- Author
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Dong X, Liu S, Zhang L, Yu S, Huo L, Qile M, Liu L, Yang B, and Yu J
- Subjects
- Animals, Cardiomegaly genetics, Cardiomegaly metabolism, Cardiomegaly pathology, Cardiomyopathies genetics, Cardiomyopathies metabolism, Cardiomyopathies pathology, Cell Proliferation drug effects, Cells, Cultured, Collagen metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Down-Regulation, Extracellular Signal-Regulated MAP Kinases metabolism, Fibroblasts drug effects, Fibroblasts metabolism, Fibroblasts pathology, Fibrosis, Male, Mice, MicroRNAs genetics, Myocardium pathology, Phosphorylation, Signal Transduction drug effects, Transfection, Ursolic Acid, Cardiomegaly prevention & control, Cardiomyopathies prevention & control, MicroRNAs metabolism, Myocardium metabolism, Triterpenes pharmacology, Ventricular Remodeling drug effects
- Abstract
Purpose: Myocardial fibrosis contributes to cardiac remodeling and loss of cardiac function in myocardial infarction and heart failure. This study used in vitro and in vivo models to examine the effects of ursolic acid (UA) on myocardial fibrosis and to explore its potential mechanism., Methods: Transverse aortic constriction (TAC) surgery was performed in mice to induce cardiac hypertrophy and fibrosis. UA was orally administered 1 week prior to TAC. Two weeks after TAC, myocardial pathology was detected using Masson's trichrome staining and transmission electron microscopy, and heart-to-body weight ratio was measured. For in vitro studies, cultured cardiac fibroblasts were treated with serum in the presence or absence of UA. The relative levels of miR-21 and p-ERK/ERK, collagen content and cell viability were measured., Results: Ursolic acid attenuated pathological cardiac hypertrophy and myocardial fibrosis in vivo induced by TAC. Downregulation of miR-21 and p-ERK/ERK were observed in myocardial fibroblasts treated with UA in a dose-dependent manner compared with the control group both in vitro and in vivo., Conclusions: Our study demonstrates that UA can inhibit myocardial fibrosis both in vitro and in vivo, and the effects of UA on myocardial fibrosis may be due to the inhibition of miR-21/ERK signaling pathways., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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