Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway

Zou,Yanting; Ma,Lili; Zhao,Yuan; Zhang,Shuncai; Zhou,Chaohui; Cai,Yu

doi:10.3892/ijmm.2017.3197

Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway

Authors:
- Yanting Zou
- Lili Ma
- Yuan Zhao
- Shuncai Zhang
- Chaohui Zhou
- Yu Cai
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Affiliations: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Xuhui, Shanghai 200032, P.R. China, Endoscopy Center, Zhongshan Hospital, Fudan University, Xuhui, Shanghai 200032, P.R. China
Published online on: October 19, 2017 https://doi.org/10.3892/ijmm.2017.3197
Pages: 430-438

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Abstract

The aim of the present study was to investigate the role of Rho kinase (also known as ROCK) inhibitor in 2,4,6-trinitrobenzene sulfonic acid induced mouse colitis; and to elucidate the underlying mechanism of ROCK1/ROCK2 inhibition in enhancing intestinal epithelial barrier (IEB) function. A specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in mouse colitis models. ROCK1 and ROCK2 were silenced respectively using RNA interference in Caco-2 cells. The expression of tight junction proteins and the downstream molecules of ROCK were assessed. Y-27632 alleviated colonic inflammation and decreased intestinal permeability. ROCK-myosin light chain (MLC) and ROCK-NF-κB pathway were activated in colitis and inhibited by Y-27632. In vitro, ROCK1 RNAi primarily downregulated the phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1) and MLC, while ROCK2 RNAi inhibited phosphorylation of nuclear factor-κB (NF-κB). In conclusion, the results suggested that the ROCK inhibitor alleviated colitis and IEB dysfunction. Inhibition of phospho-MYPT-1 and MLC by ROCK1 knockout or inhibition of NF-κB phosphorylation by ROCK2 knockout may be the underlying mechanisms.

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