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Review
. 2015 Mar 15;8(3):3089-97.
eCollection 2015.

Role of Rho kinase signal pathway in inflammatory bowel disease

Yuan Huang  1 , Shiyu Xiao  1 , Quanhang Jiang  1
Affiliations
Review

Role of Rho kinase signal pathway in inflammatory bowel disease

Yuan Huang et al. Int J Clin Exp Med. .

Abstract

Inflammatory Bowel Disease (IBD) is nonspecific inflammation in the intestinal track, including Ulcerative Colitis (UC) and Crohn's disease (CD). The incidence of IBD has increased significantly, with its numerous rising up to five million globally, more than 1,700,000 in China. Pathological character of IBD is the inflammation of intestinal mucosa and intestinal fibrosis. Although the pathogenesis of the disease has not yet been fully clarified, some evidence suggests that excessive intestinal inflammation reaction, intestinal barrier impairment and abnormal immune response can initiate IBD. As research continues, some of them have provided new insights toward understanding of Rho kinase signal pathway function at the occurrence and development of IBD. This review aims to summarize the general principles of Rho kinase signal pathway in the pathological procedure of IBD.

Keywords: IBD; Rho/Rho kinase; intestinal barrier; intestinal fibrosis.

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Figures

Figure 1
Figure 1
Regulation between ROCK and MLC. Extracellular signals initiate the activity of Rho, which then binds to Rho kinase and change GDP-Rho into GTP-Rho. Activated Rho kinase phosphorylates MLC, leading to an accumulation of pMLC. With the increasing of pMLC, it enhances stress fibrosis formation and rearranges F-actin cytoskeleton.
Figure 2
Figure 2
Cellular junctions in intestinal epithelium. It consists of TJ, AJ and desmosome. The TJ complex comprises transmembrane proteins such as occluding, claudin, JAM and intracellular proteins like ZO. The MLCK and F-actin can be regulated by Rho kinase.
Figure 3
Figure 3
Essential factors for IBD pathogenesis involves Rho signal pathway. Disruptions of the intestinal barrier result in luminal content exposure to mucosal immune cells and activate abnormal immune response, which cause pro-inflammatory cytokines increase. Simultaneously, it can damage the structure of TJ via Rho signal pathway that induced chronic inflammation.
Figure 4
Figure 4
Fibrosis in IBD involves Rho signal pathway. Misbalance of ECM induced by MMPs, TIMPs and activation of fibroblast can be induced by Rho signal pathway. This procedure is activated by the primitive inflammatory response.
See this image and copyright information in PMC

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