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
  • View Affiliations

  • 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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January 2018
Volume 41 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Zou, Y., Ma, L., Zhao, Y., Zhang, S., Zhou, C., & Cai, Y. (2018). Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway. International Journal of Molecular Medicine, 41, 430-438. https://doi.org/10.3892/ijmm.2017.3197
MLA
Zou, Y., Ma, L., Zhao, Y., Zhang, S., Zhou, C., Cai, Y."Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway". International Journal of Molecular Medicine 41.1 (2018): 430-438.
Chicago
Zou, Y., Ma, L., Zhao, Y., Zhang, S., Zhou, C., Cai, Y."Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway". International Journal of Molecular Medicine 41, no. 1 (2018): 430-438. https://doi.org/10.3892/ijmm.2017.3197