(Pro)renin receptor involves in myocardial fibrosis and oxidative stress in diabetic cardiomyopathy via the PRR-YAP pathway.
(Pro)renin receptor involves in myocardial fibrosis and oxidative stress in diabetic cardiomyopathy via the PRR-YAP pathway.
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（前）肾素受体通过PRR - YAP通路参与糖尿病心肌病中的心肌纤维化和氧化应激。
DOI：
10.1038/s41598-021-82776-2
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发表时间：
2021-02-05
影响因子：
4.6
通讯作者：
Su Q
中科院分区：
文献类型：
--
作者：
Yu S;Dong X;Yang M;Yu Q;Xiong J;Chen J;Dong B;Su Q
(Pro)肾素受体(PRR)和YAP在心血管疾病中起重要作用。然而，PRR-YAP通路在扩张型心肌病发病机制中的作用还不清楚。我们推测PRR-YAP通路可能通过触发氧化还原来促进DCM的病理损伤。Wistar大鼠心脏成纤维细胞和新生大鼠心脏成纤维细胞分别用于体内和体外研究。为了观察PRR介导的YAP通路在DCM发病机制中的作用，动物实验分为PRR过表达、PRR RNAi沉默和YAP RNAi沉默3部分。构建了携带PrR基因的重组腺病毒(Ad-PRR)、Ad-PRR-shRNA和慢病毒携带的YAP-shRNA，探讨了PrR介导的YAP在DCM发病机制中的作用。同时在心脏成纤维细胞中应用YAP特异性抑制剂维替普芬，探讨PRR-YAP通路对氧化应激和心肌纤维化的影响。结果表明，PRR过表达可促进YAP的表达，而PRR RNAi沉默可下调YAP的表达。此外，PRR过表达可加重DCM的氧化应激和心肌纤维化，而YAP拮抗剂可减轻这些病理改变。结论：PRR-YAP通路在扩张型心肌病的发病机制中起关键作用。
(Pro)renin receptor (PRR) and Yes-associated protein (YAP) play an important role in cardiovascular diseases. However, the role of PRR–YAP pathway in the pathogenesis of DCM is also not clear. We hypothesized that PRR–YAP pathway may promote pathological injuries in DCM by triggering redox. Wistar rats and neonatal rat cardiac fibroblasts were respectively used in vivo and in vitro studies. In order to observe the effects of PRR mediated YAP pathway on the pathogenesis of DCM, animal experiments were divided into 3 parts, including the evaluation the effects of PRR overexpression, PRR RNAi silencing and YAP RNAi silencing. Recombinant-adenoviruses-carried-PRR-gene (Ad-PRR), Ad-PRR-shRNA and lentivirus-carried-YAP-shRNA were constructed and the effects of PRR mediated YAP on the pathogenesis of DCM were evaluated. YAP specific inhibitor Verteporfin was also administrated in cardiac fibroblasts to explore the impact of PRR–YAP pathway on oxidative stress and myocardial fibrosis. The results displayed that PRR overexpression could enhance YAP expression but PRR RNAi silencing down-regulated its expression. Moreover, PRR overexpression could exacerbate oxidative stress and myocardial fibrosis in DCM, and these pathological changes could be rescued by YAP blockade. We concluded that PRR–YAP pathway plays a key role in the pathogenesis of DCM.
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影响因子：
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作者：
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DOI：
10.1152/ajprenal.00037.2013
发表时间：
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影响因子：
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作者：
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