LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

Abstract

As an important complication of diabetes mellitus, diabetic cardiomyopathy (DCM) is characterized by a silent development in its earlier stage and a deficient cardiomyocyte contractility in its late stage. So far, little advance has been achieved to reverse this pathological change. LncRNAs are defined as a large cluster of RNAs without the function of encoding proteins, but have the capacity in controlling gene expression. Interleukin-17 (IL-17), a proinflammatory cytokine, is a key regulator of host inflammation. Clinically, it plays a crucial role in the pathogenesis of cardiac interstitial fibrosis. In this study, we reported that high glucose-induced lncRNA-MIAT upregulation is responsible for proinflammatory IL-17 production in cardiomyocytes. The underlying mechanism is likely due to that lncRNA-MIAT specific attenuates miR-214-3p-mediated inhibitory effect on IL-17 expression. As a result, attenuated IL-17 expression significantly ameliorate cardiac fibrosis, followed by improvement of cardiac contractility. Taken together, our study first suggests that lncRNA-MIAT plays a key role in DCM and targeting lncRNA-MIAT may become a potential strategy to treat DCM.