Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis

Abstract

Background Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. Methods In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription. Results Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis. Conclusion We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.

Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy

“…Except for miR-206, the other six myomiRs, miR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499, can be expressed in cardiac muscles. Moreover, multiple studies have demonstrated that these myomiRs are involved in the development of different types of heart diseases, including dilated cardiomyopathy ( 33 ), coronary artery disease ( 34 ), cardiac hypertrophy ( 35 , 36 ), and myocardial fibrosis ( 37 , 38 ). Although miR-208a and miR-208b were not remarkably higher in the sera of cardiac involvement patients, we believe this may suggest that miR-1, miR-133a, miR-133b, and miR-499 are more sensitive to cardiac involvement.…”