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循环 miRNA 的失调促进了糖尿病性心肌病的发病机制。

Dysregulation of circulating miRNAs promotes the pathogenesis of diabetes-induced cardiomyopathy.

机构信息

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan.

出版信息

PLoS One. 2021 Apr 28;16(4):e0250773. doi: 10.1371/journal.pone.0250773. eCollection 2021.

Abstract

Diabetic Cardiomyopathy (DCM) is characterized by myocardial dysfunction caused by diabetes mellitus. After-effects of diabetic cardiomyopathy are far more lethal than non-diabetic cardiomyopathy. More than 300 million people suffer from diabetes and cardiovascular disorder which is expected to be elevated to an alarming figure of 450 million by 2030. Recent studies suggested that miRNA plays important role in the onset of diabetic cardiomyopathy. This study was designed to identify the miRNA that is responsible for the onset of diabetic cardiomyopathy using in silico and in vitro approaches. In this study, to identify the miRNA responsible for the onset of diabetic cardiomyopathy, in silico analysis was done to predict the role of these circulating miRNAs in type 2 diabetic cardiomyopathy. Shared miRNAs that are present in both diseases were selected for further analysis. Total RNA and miRNA were extracted from blood samples taken from type 2 diabetic patients as well as healthy controls to analyze the expression of important genes like AKT, VEGF, IGF, FGF1, ANGPT2 using Real-time PCR. The expression of ANGPT2 was up-regulated and AKT, VEGF, IGF, FGF1 were down-regulated in DCM patients as compared to healthy controls. The miRNA expression of miR-17 was up-regulated and miR-24, miR-150, miR-199a, miR-214, and miR-320a were down-regulated in the DCM patients as compared to healthy controls. This shows that dysregulation of target genes and miRNA may contribute towards the pathogenesis of DCM and more studies should be conducted to elucidate the role of circulating miRNAs to use them as therapeutic and diagnostic options.

摘要

糖尿病心肌病(DCM)的特征是由糖尿病引起的心肌功能障碍。糖尿病性心肌病的后遗症比非糖尿病性心肌病更为致命。目前全球有超过 3 亿人患有糖尿病和心血管疾病,预计到 2030 年这一数字将上升到令人震惊的 4.5 亿。最近的研究表明,miRNA 在糖尿病性心肌病的发病中起重要作用。本研究旨在通过计算机模拟和体外方法确定导致糖尿病性心肌病发病的 miRNA。在这项研究中,为了确定导致糖尿病性心肌病发病的 miRNA,通过计算机模拟分析预测这些循环 miRNA 在 2 型糖尿病性心肌病中的作用。选择两种疾病都存在的共享 miRNA 进行进一步分析。从 2 型糖尿病患者和健康对照者的血液样本中提取总 RNA 和 miRNA,使用实时 PCR 分析 AKT、VEGF、IGF、FGF1、ANGPT2 等重要基因的表达。与健康对照组相比,DCM 患者的 ANGPT2 表达上调,AKT、VEGF、IGF、FGF1 表达下调。与健康对照组相比,DCM 患者的 miR-17 表达上调,miR-24、miR-150、miR-199a、miR-214 和 miR-320a 表达下调。这表明靶基因和 miRNA 的失调可能导致 DCM 的发病机制,应进行更多的研究以阐明循环 miRNA 的作用,将其作为治疗和诊断选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b22/8081166/c6d5f6dd640d/pone.0250773.g001.jpg

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