Mecp2 protects kidney from ischemia-reperfusion injury through transcriptional repressing IL-6/STAT3 signaling.
Mecp2 protects kidney from ischemia-reperfusion injury through transcriptional repressing IL-6/STAT3 signaling.
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Mecp2 通过转录抑制 IL-6/STAT3 信号传导保护肾脏免受缺血再灌注损伤
DOI：
10.7150/thno.72515
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发表时间：
2022
期刊：
影响因子：
12.4
通讯作者：
Huang, Kun
中科院分区：
文献类型：
--
作者：
Wang, Jiao;Xiong, Mingrui;Fan, Yu;Liu, Chengyu;Wang, Qing;Yang, Dong;Yuan, Yangmian;Huang, Yixue;Wang, Shun;Zhang, Yu;Niu, Shuxuan;Yue, Junqiu;Su, Hua;Zhang, Chun;Chen, Hong;Zheng, Ling;Huang, Kun
原理：缺血再灌注（IR）诱导的急性肾损伤（AKI）导致与高发病率和高死亡率相关的严重临床问题。Mecp2是一种甲基 - CpG结合蛋白，其突变或缺失会导致一种名为瑞特综合征的神经发育疾病。值得注意的是，一些瑞特综合征患者存在泌尿系统功能障碍。目前尚不清楚Mecp2是否以及如何影响AKI。
方法：利用肾小管细胞特异性Mecp2缺失小鼠并对其施加IR损伤，以研究Mecp2对肾小管损伤、功能、细胞死亡、纤维化和炎症的影响。用野生型或Mecp2不同结构域缺失突变体转染培养的肾上皮细胞系，以研究Mecp2对Il - 6/STAT3信号通路的影响。
结果：我们的结果表明，在体内和体外急性肾损伤时Mecp2迅速上调。值得注意的是，在AKI患者的肾切片中也发现肾小管MeCP2染色增强。此外，Mecp2的缺失加重了肾损伤，并促进了肾细胞死亡、炎症和纤维化。从机制上讲，Mecp2通过其转录抑制结构域与促炎细胞因子Il - 6的启动子结合，负向调节其表达，从而抑制STAT3的激活。
结论：研究表明Mecp2通过抑制Il - 6/STAT3轴对AKI具有一种新的保护作用。
Rationale: Ischemia-reperfusion (IR) induced acute kidney injury (AKI) causes serious clinical problems associated with high morbidity and mortality. Mecp2 is a methyl-CpG binding protein, its mutation or deletion causes a neurodevelopment disease called Rett syndrome. Notably, some Rett syndrome patients present urological dysfunctions. It remains unclear whether and how Mecp2 affects AKI. Methods: Renal tubular cell specific Mecp2 deletion mice challenged with IR injury were used to investigate the effects of Mecp2 on renal tubular damage, function, cell death, fibrosis and inflammation. Cultured renal epithelial cell lines were transfected with wildtype or different domain-deletion mutants of Mecp2 to study the effects of Mecp2 on Il-6/STAT3 signaling. Results: Our results indicated rapidly upregulated Mecp2 upon acute in vivo and in vitro renal injury. Notably, increased tubular MeCP2 staining was also found in the renal sections of AKI patients. Furthermore, ablation of Mecp2 aggravated renal injury, and promoted renal cell death, inflammation, and fibrosis. Mechanistically, through its transcriptional repression domain, Mecp2 bound to the promoter of proinflammatory cytokine Il-6 to negatively regulate its expression, thus inhibiting STAT3 activation. Conclusions: A novel protective role of Mecp2 against AKI via repressing the Il-6/STAT3 axis was suggested.
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影响因子：
13.6
作者：
Kielar, ML;John, R;Lu, CY
通讯作者：
Lu, CY
影响因子：
32.4
作者：
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影响因子：
2.5
作者：
ADLER, DA;QUADERI, NA;DISTECHE, CM
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DISTECHE, CM
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DOI：
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发表时间：
2015-07-01
影响因子：
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作者：
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影响因子：
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