Cardiac fibrosis is a pathological remodeling response to myocardial infarction (MI) and impairs cardiac contractility. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in patients with MI. However, the functions of MALAT1 in cardiac fibrosis have not been elucidated. This study elucidates the roles of MALAT1 in MI and the underlying mechanisms. The MI model was established by artificial coronary artery occlusion in mice. Western blot analysis and quantitative reverse transcription-polymerase chain reaction were performed to analyze protein expression and RNA expression, respectively. Cardiac function was measured by echocardiography. Masson's trichrome staining was used to exhibit the fibrotic area in MI hearts. Cardiac fibroblasts were isolated from newborn pups, and cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Upregulation of MALAT1 and downregulation of microRNA-145 (miR-145) were induced in MI heart and angiotensin II (AngII)-treated cardiac fibroblasts, and the inhibition of miR-145 expression was reversed by MALAT1 depletion. Knockdown MALAT1 ameliorated MI-impaired cardiac function and prevented AngII-induced fibroblast proliferation, collagen production, and α-SMA expression in cardiac fibroblasts. MALAT1 stability and transforming growth factor-β1 (TGF-β1) activity were regulated by miR-145. AngII-induced TGF-β1 activity in cardiac fibroblasts was blocked by MALAT1 knockdown. Based on these results, we concluded that lncRNA MALAT1 promotes cardiac fibrosis and deteriorates cardiac function post-MI by regulating TGF-β1 activity via miR-145.
Keywords: MALAT1; TGF-β1; fibrosis; miR-145; myocardial infarction.
© 2018 Wiley Periodicals, Inc.