Abstract
Objective: Diabetic cardiomyopathy (DCM) is one of the complications experienced by patients with diabetes. In recent years, long noncoding RNAs (lncRNAs) have been investigated because of their role in the progression of various diseases, including DCM. The purpose of the present study was to explore the role of lncRNA GAS5 in high glucose (HG)-induced cardiomyocyte injury and apoptosis.Materials and methods: We constructed HG-induced AC16 cardiomyocytes and a streptozotocin (STZ)-induced rat diabetes model. GAS5 was overexpressed and knocked out at the cellular level, and GAS5 was knocked down by lentiviruses at the animal level to observe its effect on myocardial injury. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of GAS5. Cell proliferation and apoptosis after GAS5 knockout were detected by CCK-8, TUNEL, and flow cytometry assays. ELISA was used to detect the changes in myocardial enzyme content in cells and animal myocardial tissues during the action of GAS5 on myocardial injury.Results: GAS5 expression was up-regulated in HG-treated AC16 cardiomyocytes and the rat diabetic myocardial injury model. The down-regulation of GAS5 could inhibit HG-induced myocardial damage. This work proved that the down-regulation of GAS5 could reverse cardiomyocyte injury and apoptosis by targeting miR-138 to down-regulate CYP11B2.Conclusion: We confirmed for the first time that the down-regulation of GAS5 could reverse CYP11B2 via the miR-138 axis to reverse HG-induced cardiomyocyte injury. This research might provide a new direction for explaining the developmental mechanism of DCM and potential targets for the treatment of myocardial injury.
Highlights
Diabetes is a metabolic syndrome that seriously threatens human health worldwide [1]
Our study aims to determine the role of long noncoding RNA (lncRNA) GAS5 in the progression of diabetic cardiomyopathy (DCM) and how the mechanism of Competitive endogenous RNA (ceRNA) contributes to high glucose (HG)-induced cardiomyocyte injury
The present study showed that GAS5 expression was up-regulated in HG-treated AC16 cardiomyocytes and a rat diabetic myocardial injury model
Summary
Diabetes is a metabolic syndrome that seriously threatens human health worldwide [1]. More than 371 million people are affected currently [2]. The International Diabetes Federation predicts that the number of patients with diabetes will increase to 552 million by 2030 [3]. Its pathogenesis has been proposed from a molecular and cellular perspective and may involve excessive oxidative stress, fibrosis, apoptosis, and inflammation caused by hyperglycemia, controversy remains [6,7,8]. Specific biomarkers for diabetic cardiomyopathy (DCM) and treatment options that can prevent disease progression do not exist. An urgent need to study the pathogenesis of DCM deeply exists. In recent years, noncoding RNAs (ncRNAs) have been found to be widely involved in regulating the disease progression of DCM [9,10]
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