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Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease
Authors:Xuewen Wang  Shuhua Chen  Hong Xiang  Ziwei Liang  Hongwei Lu
Affiliation:1. Center for Experimental Medicine, the Third Xiangya Hospital of Central South University, Changsha, China

Department of Cardiology, the Third Xiangya Hospital of Central South University, Changsha, China

Contribution: Conceptualization (equal), ​Investigation (lead), Resources (equal), Writing - review & editing (lead);2. Department of Biochemistry, School of Life Sciences of Central South University, Changsha, China

Contribution: Funding acquisition (lead), Supervision (equal);3. Center for Experimental Medicine, the Third Xiangya Hospital of Central South University, Changsha, China

Contribution: ​Investigation (supporting), Resources (equal);4. Department of Clinical laboratory, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, China

Contribution: ​Investigation (supporting), Resources (equal);5. Center for Experimental Medicine, the Third Xiangya Hospital of Central South University, Changsha, China

Abstract:
Sphingosine-1-phosphate receptors (S1PRs) have an impact on the intestinal inflammation of inflammatory bowel disease (IBD) by regulating lymphocyte migration and differentiation. S1PR modulators as an emerging therapeutic approach are being investigated for the treatment of IBD. However, the role of S1PRs in intestinal vessels has not drawn much attention. Intestinal vascular damage is one of the major pathophysiological features of IBD, characterized by increased vascular density and impaired barrier function. S1PRs have pleiotropic effects on vascular endothelial cells, including proliferation, migration, angiogenesis and barrier homeostasis. Mounting evidence shows that S1PRs are abnormally expressed on intestinal vascular endothelial cells in IBD. Unexpectedly, S1PR modulators may damage intestinal vasculature, for example increase intestinal bleeding; therefore, S1PRs are thought to be involved in the regulation of intestinal vascular function in IBD. However, little is understood about how S1PRs regulate intestinal vascular function and participate in the initiation and progression of IBD. In this review, we summarize the pathogenic role of S1PRs in and the underlying mechanisms behind the intestinal vascular injury in IBD in order for improving IBD practice including S1PR-targeted therapies.
Keywords:inflammatory bowel disease  lymphocyte  sphingosine-1-phosphate receptor  vascular injury
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