MBNL1 Regulates Myocardial Remodeling Through Myocardin

Background: Myocardial remodeling is a common phenomenon in cardiovascular diseases, which threatens human health and quality of life. To develop effective early diagnosis and treatment methods, the molecular mechanism of myocardial remodeling should be explored in depth. Methods: Expression of muscleblind like splicing regulator 1 (MBNL1) was analyzed in cardiomyocytes of cardiac hypertrophy model and normal mice. Western blot, realtime RT-PCR, Immunofluorescence, hematoxylin-eosin staining (HE), and other experiments were performed to determine whether MBNL1 contributes to isoprenaline (ISO)-induced myocardial remodeling and regulates Myocardin expression in vivo and in vitro. RNA Immunoprecipitation (RIP), luciferase report, RNA pulldown and other assays were employed to define the underlying regulatory mechanisms. Different stages of myocardial remodeling mouse models were was utilized to examine whether MBNL1 can be a potential diagnostic target for cardiac remodeling. Findings: In this study, we found that MBNL1 was highly expressed in the cardiac hypertrophy model compared with the normal group by analyzing the sequencing data in the GEO database. Then, the overexpression of MBNL1 promoted ISO induced cardiac hypertrophy and fibrosis by stabilizing Myocardin mRNA was confirmed. Moreover, the rise of MBNL1 mRNA level could be detected in the peripheral blood of different degrees of cardiac remodeling model induced by ISO. Interestingly, Myocardin could reverse activate the expression of MBNL1. Interpretation: These results suggest that MBNL1 may be a potential target for early diagnosis or clinical treatment of myocardial remodeling. Funding Statement: This work was supported by the National Natural Science Foundation of China (No.31570764). Declaration of Interests: All authors have declare no conflict interests. Ethics Approval Statement: The animal experiments performed in this investigation were approved by the Institutional Animal Care and Use Committee of the Tianyou Hospital Affiliated to Wuhan University of Science and Technology and complied with the ethical standards outlined in the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, publication No. 85-23).