Snai1-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation.
Snai1-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation.
复制标题
DOI：
10.1038/s41419-020-03322-y
复制
发表时间：
2021-01-05
影响因子：
9
通讯作者：
Zhu T
中科院分区：
文献类型：
--
作者：
Qi R;Wang J;Jiang Y;Qiu Y;Xu M;Rong R;Zhu T
Renal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial–mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT and cell cycle arrest, and elucidate the underlying mechanism. We examined human kidney allograft samples with interstitial fibrosis and three mice renal fibrosis models, unilateral ureter obstruction (UUO), ischemia–reperfusion injury, and Adriamycin nephropathy. The partial EMT process and p53–p21 axis were elevated in both human allograft with interstitial fibrosis, as well as three mice renal fibrosis models, and showed a time-dependent increase as fibrosis progressed in the UUO model. Snai1 controlled the partial EMT process, and led to parallel changes in renal fibrosis, G2/M arrest, and inflammation. p53–p21 axis arrested cell cycle at G2/M, and prompted partial EMT and fibrosis together with inflammation. NF-κB inhibitor Bay11-7082 disrupted the reciprocal loop between Snai1-induced partial EMT and p53–p21-mediated G2/M arrest. We demonstrated the reciprocal loop between partial EMT and G2/M arrest of TECs during renal fibrogenesis and revealed NF-κB-mediated inflammatory response as the underlying mechanism. This study suggests that targeting NF-κB might be a plausible therapeutic strategy to disrupt the reciprocal loop between partial EMT and G2/M arrest, therefore alleviating renal fibrosis.
登录
查看更多内容
诱导和量化细胞衰老的技术。
DOI：
10.3791/55533
发表时间：
2017-05-01
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Noren Hooten N;Evans MK
通讯作者：
Evans MK
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
4.8
作者：
Overstreet JM;Samarakoon R;Meldrum KK;Higgins PJ
通讯作者：
Higgins PJ
成纤维细胞生长因子 21 通过激活 AKT 负调节 TGF-β-p53-Smad2/3 介导的上皮间质转化，从而减轻糖尿病引起的肾纤维化
影响因子：
5.9
作者：
Lin, Sundong;Yu, Lechu;Zhang, Chi
通讯作者：
Zhang, Chi
影响因子：
4.6
作者：
Lee J;Rhee MH;Kim E;Cho JY
通讯作者：
Cho JY