氮氧化物4
上皮-间质转换
P22phox公司
化学
NADPH氧化酶
细胞生物学
癌症研究
氧化应激
细胞凋亡
下调和上调
肾
内分泌学
内科学
医学
生物
生物化学
基因
作者
Xiaohong Sun,Haiming Xiao,Shanshan Li,Rui Chen,Zeyuan Lin,Yan Yang,Zhiquan Chen,Li Deng,Heqing Huang
标识
DOI:10.1016/j.phrs.2022.106084
摘要
Renal tubulointerstitial fibrosis (RIF), characterized by epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs), is the main cause of diabetic renal fibrosis. Oxidative stress plays a pivotal role in the development of diabetic RIF. Connexin32 (Cx32), prominently expressed in renal TECs, has emerged as an important player in the regulation of oxidative stress. However, the role of Cx32 in diabetic RIF has not been explored yet. Here, we showed that adenovirus-mediated Cx32 overexpression suppressed EMT to ameliorate RIF and renal function in STZ-induced diabetic mice, while knockout (KO) of Cx32 exacerbated RIF in diabetic mice. Moreover, overexpression of Cx32 inhibited EMT and the production of extra cellular matrix (ECM) in high glucose (HG) induced NRK-52E cells, whereas knockdown of Cx32 showed the opposite effects. Furthermore, we showed that NOX4, the main source of ROS in renal tubular, was down-regulated by Cx32. Mechanistically, Cx32 down-regulated the expression of PKC alpha in a carboxyl-terminal-dependent manner, thereby inhibiting the phosphorylation at Thr
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