MiR-207 inhibits autophagy and promotes apoptosis of cardiomyocytes by directly targeting LAMP2 in type 2 diabetic cardiomyopathy
MiR-207 inhibits autophagy and promotes apoptosis of cardiomyocytes by directly targeting LAMP2 in type 2 diabetic cardiomyopathy
复制标题
MiR-207直接靶向LAMP2抑制2型糖尿病心肌病自噬并促进心肌细胞凋亡
DOI：
10.1016/j.bbrc.2019.09.092
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发表时间：
2019-11-26
影响因子：
3.1
通讯作者：
Han, Yaling
中科院分区：
文献类型：
--
作者：
Xing, Ruinan;Liu, Dan;Han, Yaling
自噬功能障碍在糖尿病心肌病(DCM)中起重要作用。MIR-207调节缺血性卒中后神经细胞自噬相关蛋白溶酶体相关膜蛋白2(LAMP2)的表达。然而，miR-207在扩张型心肌病中的作用和机制仍不清楚。因此，本研究旨在探讨miR-207在2型DCM中的作用和机制。结果显示，在2型DCM小鼠和PA刺激的新生小鼠心肌细胞中，存在自噬功能障碍，表现为Lc3II和p62表达增加，LAMP2表达降低，细胞凋亡增加，caspase3表达上调。此外，miR-207在DCM小鼠和PA刺激的NMCMS中显著上调。在NMCM中，miR-207抑制LAMP2基因和蛋白的表达。MIR-207模拟物通过增加p62和LC3II的表达抑制自噬，通过增加裂解的caspase3表达促进细胞的凋亡，这些作用被LAMP2的过表达逆转。结论：miR-207通过直接靶向LAMP2抑制心肌细胞自噬，促进心肌细胞凋亡，参与了2型糖尿病心肌病变的发生发展。(C)2019 Elsevier Inc.保留所有权利。
Autophagy dysfunction plays a critical role in diabetic cardiomyopathy (DCM). MiR-207 regulates the expression of lysosomal-associated membrane protein 2 (LAMP2), an autophagy-related protein, following ischemic stroke in neurocytes. However, the roles and mechanisms of miR-207 in DCM remain unknown. Therefore, in this study, we aim to investigate the roles and mechanisms of miR-207 in type 2 DCM. The results showed that autophagic dysfunction with increased LC3II and P62 expression and decreased LAMP2 expression, and increased cell apoptosis with up-regulated cleaved-caspase3 expression were noted in the myocardium of type 2 DCM mice and neonatal mouse cardiac myocytes (NMCMs) stimulated with PA. In addition, miR-207 was significantly upregulated in the myocardium of DCM mice and NMCMs stimulated with PA. In NMCMs, miR-207 inhibited LAMP2 mRNA and protein expression. MiR-207 mimics significantly inhibited autophagy by increasing P62 and LC3II expression and promoted cell apoptosis by increasing cleaved-caspase3 expression, and these effects were reversed by LAMP2 overexpression. In conclusion, miR-207 inhibited autophagy and promoted apoptosis of cardiomyocytes by directly targeting LAMP2, which participated in the development of type 2 diabetic cardiomyopathy. (C) 2019 Elsevier Inc. All rights reserved.