The protective microRNA-199a-5p-mediated unfolded protein response in hypoxic cardiomyocytes is regulated by STAT3 pathway
The protective microRNA-199a-5p-mediated unfolded protein response in hypoxic cardiomyocytes is regulated by STAT3 pathway
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缺氧心肌细胞中保护性 microRNA-199a-5p 介导的未折叠蛋白反应受 STAT3 通路调节
DOI：
10.1007/s13105-018-0657-6
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发表时间：
2018-11
影响因子：
3.4
通讯作者：
Li Peng
中科院分区：
文献类型：
--
作者：
Zhou Yang;Pang Bo;Xiao Yingbin;Zhou Simin;He Bin;Zhang Fan;Liu Wei;Peng Huali;Li Peng
下调miR-199 a-5 p对缺血和缺氧心肌细胞的保护作用已被广泛认可，但其潜在机制尚不清楚。本研究探讨了缺氧心肌细胞中信号转导子和转录激活子3（STAT 3）信号转导增强与miR-199 a-5 p产生降低之间的关系。本研究首次发现了先天性心脏病患儿缺氧心肌标本中白细胞介素（IL）-6和IL-11升高，以及随后STAT 3信号转导激活与miR-199 a-5 p下调之间的相关性。然后，利用缺氧小鼠模型，通过磷酸化STAT 3（pSTAT 3）的干预，观察pSTAT 3对miR-199 a-5 p表达的影响，并调节其靶基因内质网应激相关转录激活因子6（ATF 6）和78 kDa葡萄糖调节蛋白（GRP 78）的表达。进一步观察发现，心肌组织中的pSTAT 3信号可以影响miR-199 a-5 p的前体pri-miR-199 a-2的表达。染色质免疫沉淀（ChIP）实验也证实了pSTAT 3能够与miR-199 a-2基因启动子区结合，且在低氧条件下结合更为显著。总之，在慢性缺氧期间心肌细胞中STAT 3信号的激活导致miR-199 a-5 p的下调，其促进许多下游靶基因的表达。这是缺氧时心肌适应性保护机制中的一个重要途径。
The protective effects of downregulated miR-199a-5p on ischemic and hypoxic cardiomyocytes were well recognized, but the underlying mechanism of inhibited miR-199a-5p is not yet clear. The present study explored the relationship between enhanced signal transducer and activator of transcription 3 (STAT3) signaling and lowered production of miR-199a-5p in hypoxic cardiomyocytes. This study firstly found the correlation between elevated interleukin (IL)-6 and IL-11, as well as subsequent STAT3 signaling activation and the downregulation of miR-199a-5p in hypoxic myocardial samples from children with congenital heart disease. Then, using model of hypoxic mice and the intervention of phosphorylated STAT3 (pSTAT3), it was observed that pSTAT3 affected the expression of miR-199a-5p and modulated the expression of its target genes, including endoplasmic reticulum stress (ERS)-related activating transcription factor 6 (ATF6) and 78 kDa glucose-regulated protein (GRP78). Further observation revealed that the pSTAT3 signal in cardiac tissue could affect the expression of pri-miR-199a-2, a precursor of miR-199a-5p. And the chromatin immunoprecipitation (ChIP) assay also confirmed that pSTAT3 could bind to the promoter region of miR-199a-2 gene, which is more significant under hypoxic conditions. In conclusion, the activation of STAT3 signaling in cardiomyocytes during chronic hypoxia leads to downregulation of miR-199a-5p, which promotes the expression of many downstream target genes. This is an important pathway in the adaptive protection mechanism of myocardium during hypoxia.
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影响因子：
20.1
作者：
Rane S;He M;Sayed D;Vashistha H;Malhotra A;Sadoshima J;Vatner DE;Vatner SF;Abdellatif M
通讯作者：
Abdellatif M
microRNA-199a-5p 保护肝细胞免受胆汁酸诱导的持续内质网应激
影响因子：
9
作者：
通讯作者：
--
miR-146a在人肝癌细胞中受STAT3直接调控并参与抗肿瘤免疫抑制
影响因子：
4.3
作者：
Sun, Xiaoxia;Zhang, Jian;Tian, Zhigang
通讯作者：
Tian, Zhigang
影响因子：
11.2
作者：
B. Dai;J. Meng;M. Peyton;L. Girard;W. Bornmann;L. Ji;J. Minna;B. Fang;J. Roth
通讯作者：
B. Dai;J. Meng;M. Peyton;L. Girard;W. Bornmann;L. Ji;J. Minna;B. Fang;J. Roth
Elatoside C 通过减少内质网应激来防止 H9c2 心肌细胞缺氧/复氧诱导的细胞凋亡，部分取决于 STAT3 激活
影响因子：
7.2
作者：
Wang, Min;Meng, Xiang-bao;Sun, Xiao-bo
通讯作者：
Sun, Xiao-bo