Effects of (Pro)renin Receptor on Diabetic Cardiomyopathy Pathological Processes in Rats via the PRR-AMPK-YAP Pathway.
Effects of (Pro)renin Receptor on Diabetic Cardiomyopathy Pathological Processes in Rats via the PRR-AMPK-YAP Pathway.
复制标题
肾素原受体通过 PRR-AMPK-YAP 通路对大鼠糖尿病心肌病病理过程的影响
DOI：
10.3389/fphys.2021.657378
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发表时间：
2021
影响因子：
4
通讯作者：
Su Q
中科院分区：
文献类型：
--
作者：
Xiong J;Dong X;Li S;Jiang F;Chen J;Yu S;Dong B;Su Q
糖尿病性心肌病（DCM）是糖尿病常见的并发症。肾素受体（PRR）是局部组织肾素-血管紧张素系统的重要成员，在许多心血管疾病中起重要作用。是相关蛋白（雅普）在许多心血管疾病中也起着至关重要的作用。然而，PRR和雅普对DCM的作用机制尚不清楚。本研究的目的是确定PRR在DCM病理进展中的作用以及PRR是否通过雅普影响糖尿病心肌病的病理过程。我们首次建立了糖尿病心肌病大鼠模型，下调PRR的表达，上调和下调雅普的表达。然后测量心肌炎症和纤维化水平，并评估心功能。体外培养原代大鼠心脏成纤维细胞（CFs），观察AMPK对高糖培养CFs增殖的影响。在体外测量炎症和纤维化的水平。结果显示PRR和雅普沉默可减轻心肌炎症和纤维化。GSK 621阻断PRR对AMPK和雅普的作用，并改善CF炎症和纤维化。PRR表达的抑制为DCM的治疗提供了新的治疗策略。PRR可能通过PRR-AMPK-雅普通路参与DCM的病理过程。
Diabetic cardiomyopathy (DCM) is a common complication associated with diabetes. The (pro)renin receptor (PRR) is an important member of the local tissue renin-angiotensin system and plays a vital role in many cardiovascular diseases. Yes-associated protein (YAP) also plays a crucial role in many cardiovascular diseases. However, the mechanism responsible for the effects of PRR and YAP on DCM remains unclear. The purpose of this study was to determine the role of PRR in the pathological progression of DCM and whether PRR influences the pathological processes of diabetic cardiomyopathy through YAP. We first established diabetic cardiomyopathy rats model, downregulated the expression of PRR, and upregulated and downregulated the expression of YAP. The levels of myocardial inflammation and fibrosis were then measured and cardiac function was evaluated. In vitro, primary rat cardiac fibroblasts (CFs) were cultured with high glucose, with or without transfection with recombinant adenovirus expressing PRR, and GSK621 was used to observe the effect of AMPK. The levels of inflammation and fibrosis were measured in vitro. The results showed that PRR and YAP silencing alleviated myocardial inflammation and fibrosis. GSK621 blocked the effect of PRR on AMPK and YAP and improved CF inflammation and fibrosis. The inhibition of PRR expression offers a new therapeutic strategy for the treatment of DCM. The effects of PRR on the pathological process of DCM in rats may be mediated via the PRR-AMPK-YAP pathway.
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DOI：
10.1161/atvbaha.112.254730
发表时间：
2012-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Wang X;Hu G;Gao X;Wang Y;Zhang W;Harmon EY;Zhi X;Xu Z;Lennartz MR;Barroso M;Trebak M;Chen C;Zhou J
通讯作者：
Zhou J
影响因子：
3.7
作者：
Akhtar, Safia;Siragy, Helmy M.
通讯作者：
Siragy, Helmy M.
影响因子：
19.6
作者：
Nguyen, G;Delarue, F;Sraer, JD
通讯作者：
Sraer, JD
DOI：
10.1158/1541-7786.mcr-17-0023
发表时间：
2017-07
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Hao F;Xu Q;Zhao Y;Stevens JV;Young SH;Sinnett-Smith J;Rozengurt E
通讯作者：
Rozengurt E
影响因子：
4.9
作者：
Connelly, Kim A.;Advani, Andrew;Gilbert, Richard E.
通讯作者：
Gilbert, Richard E.