Role of ROCK/NF-κB/AQP8 signaling in ethanol-induced intestinal epithelial barrier dysfunction

被引：7
作者：
Zhao, Hang [1 ]
Sun, Xiaonan [2 ]
Tong, Jing [1 ]
机构：
[1] China Med Univ, Affiliated Hosp 1, Dept Gastroenterol, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China
[2] 4 Peoples Hosp Shenyang, Dept Ophthalmol, Shenyang 110031, Liaoning, Peoples R China
来源：
MOLECULAR MEDICINE REPORTS | 2020年 / 22卷 / 03期
基金：
中国国家自然科学基金;
关键词：
ROCK; NF-kappa B; AQP8; ethanol; IEB; NF-KAPPA-B; ENDOTHELIAL-CELLS; INDUCED INCREASE; ACTIVATION; EXPRESSION; PHOSPHORYLATION; INFLAMMATION; RHOA; MLC;
D O I：
10.3892/mmr.2020.11318
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The present study aimed to investigate the signaling pathways and the underlying molecular mechanisms involved in ethanol-induced intestinal epithelial barrier (IEB) dysfunction. Therefore, an in vitro experimental model of IEB was established using an ethanol-treated Caco-2 intestinal epithelial cell monolayer. The results confirmed that Rho-associated kinases (ROCKs), namely ROCK1 and ROCK2, were involved in the underlying pathway of ethanol-induced IEB dysfunction. Ethanol exposure significantly increased the expression of both ROCK isoforms and the activity of nuclear factor kappa B (NF-kappa B). Furthermore, ROCK1- and ROCK2-specific small interfering RNAs (siRNAs), and the NF-kappa B inhibitor ammonium pyrrolidine dithiocarbamate partially inhibited transepithelial electrical resistance in Caco-2 cells in an in vitro IEB model. In addition, ROCK1- and ROCK2-specific siRNAs inhibited the activity of NF-kappa B, thereby downregulating the expression of aquaporin 8 (AQP8). Taken together, the results of the present study suggested that ROCK1/ROCK2-mediated activation of NF-kappa B and upregulation of AQP8 expression levels may represent a novel mechanism of ethanol-induced impairment of IEB function.
引用
收藏
页码：2253 / 2262
页数：10
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