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Myosin Light Chain Kinase Inhibitor Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice

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Abstract

Background and Aims

Myosin light chain kinase (MLCK) plays a central role in the mechanisms of barrier dysfunction, and intestinal epithelial MLCK protein expression is upregulated in active ulcerative colitis (UC). ML-7, a MLCK inhibitor, has been used in many MLCK studies. However, the effect of ML-7 has never been estimated in colitis models. The aim of this study was to determine whether ML-7 can treat UC.

Methods

Experimental colitis was induced and ML-7 was administered by intraperitoneal injection. The disease activity index (DAI) scores were evaluated and colon tissue was collected for the assessment of histological changes, myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-13 and interleukin (IL)-17 levels. The small intestinal mucosa was ultrastructurally examined, epithelial MLCK protein expression and enzymatic activity were determined, and intestinal permeability was assayed using FITC-dextran 4000 (FD-4) and Evans blue (EB).

Results

ML-7 was found to be significantly effective in reducing the DAI scores and histological index scores, and decreasing MPO activity and TNF-α, IFN-γ, IL-13 and IL-17 levels. The small intestinal epithelial MLCK protein expression and enzymatic activity were downregulated by ML-7. The epithelial cells and intercellular tight junctions were ameliorated, and the amount of FD-4 in blood and EB permeating into the intestine were decreased by ML-7 in colitis mice.

Conclusions

ML-7 has a significant anti-colitis effect in colitis mice. It is mainly associated with the inhibition of the epithelial MLCK protein expression, resulting in ameliorated intestinal mucosal permeability.

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Acknowledgments

Supported by a grant from the First Affiliated Hospital of Anhui Medical University. We thank Professor Ke Chen, Professor Wen Hu and Professor Daobing Wang for assistance with pathological technology, and we also thank Yuxian Shen, MD, PhD, Yongmei Hu, MD, Jiajia Wang, MD, and Qing Zhou, MD, for their support during the study.

Conflict of interest

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, The Key Laboratory of Digestive Diseases of Anhui Province, No. 218 Jixi Road, Hefei, Anhui, 230022, China

    Xiaochang Liu, Jianming Xu, Qiao Mei, Liang Han & Jian Huang

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  1. Xiaochang Liu
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Correspondence to Jianming Xu.

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Liu, X., Xu, J., Mei, Q. et al. Myosin Light Chain Kinase Inhibitor Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice. Dig Dis Sci 58, 107–114 (2013). https://doi.org/10.1007/s10620-012-2304-3

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  • DOI: https://doi.org/10.1007/s10620-012-2304-3

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