Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Biosci Rep. 2021 Sep 30;41(9). doi: 10.1042/BSR20202232.
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.
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.
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.
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.
糖尿病心肌病（DCM）是糖尿病患者的并发症之一。近年来，长链非编码 RNA（lncRNA）因其在包括 DCM 在内的各种疾病的进展中的作用而受到研究。本研究旨在探讨 lncRNA GAS5 在高葡萄糖（HG）诱导的心肌细胞损伤和凋亡中的作用。
我们构建了 HG 诱导的 AC16 心肌细胞和链脲佐菌素（STZ）诱导的大鼠糖尿病模型。在细胞水平上过表达和敲除 GAS5，并在动物水平上通过慢病毒敲低 GAS5，观察其对心肌损伤的影响。实时定量聚合酶链反应（RT-qPCR）检测 GAS5 的表达。CCK-8、TUNEL 和流式细胞术检测 GAS5 敲除后细胞增殖和凋亡情况。ELISA 检测 GAS5 作用于心肌损伤时细胞和动物心肌组织中心肌酶含量的变化。
HG 处理的 AC16 心肌细胞和大鼠糖尿病心肌损伤模型中 GAS5 表达上调。GAS5 的下调可抑制 HG 诱导的心肌损伤。本工作证明，通过靶向 miR-138 下调 CYP11B2，下调 GAS5 可逆转 HG 诱导的心肌细胞损伤和凋亡。
我们首次证实，下调 GAS5 可通过 miR-138 轴逆转 CYP11B2，从而逆转 HG 诱导的心肌细胞损伤。这项研究可能为解释 DCM 的发育机制和心肌损伤的潜在治疗靶点提供新的方向。
