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

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          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.

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          Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels

          Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals. In this review, we summarize the functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels.
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            lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA.

            Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus-induced microvascular dysfunction is largely unknown.
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              Diabetic cardiomyopathy: pathophysiology and clinical features

              Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation–contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                15 April 2020
                2020
                : 8
                : 243
                Affiliations
                [1] 1Department of Cardiovascular Surgery, Ningbo First Hospital , Ningbo, China
                [2] 2Department of Vascular Surgery, School of Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University , Hangzhou, China
                Author notes

                Edited by: Li Qian, University of North Carolina at Chapel Hill, United States

                Reviewed by: Yaozu Xiang, Tongji University, China; Feng Zhu, College of Pharmaceutical Science, Zhejiang University, China

                *Correspondence: Xupin Xie, xiexupin@ 123456163.com

                This article was submitted to Molecular Medicine, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00243
                7174588
                32351959
                b095a97f-0661-4e93-8afa-1fb2b6e34184
                Copyright © 2020 Qi, Wu, Mai, Lin, Shen, Zhang, Gao, Mao and Xie.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 January 2020
                : 23 March 2020
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 38, Pages: 13, Words: 0
                Categories
                Cell and Developmental Biology
                Original Research

                diabetic cardiomyopathy,il-17,lncrna-miat,mir-214-3p,fibrosis

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