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Review
. 2021 Mar;25(6):2740-2749.
doi: 10.1111/jcmm.16333. Epub 2021 Feb 17.

Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease

Xuewen Wang  1   2 , Shuhua Chen  3 , Hong Xiang  1 , Ziwei Liang  4 , Hongwei Lu  1   2
Affiliations
Review

Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease

Xuewen Wang et al. J Cell Mol Med. 2021 Mar.

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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Conflict of interest statement

The authors confirm that there are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Low levels of ER stress/ROS stimulate angiogenesis, whereas high levels of ER stress/ROS inhibit angiogenesis
FIGURE 2
FIGURE 2
S1PRs may mediate intestinal angiogenesis of IBD by regulating ROS, ER stress, glycolysis and VEGF signal pathway
FIGURE 3
FIGURE 3
S1PRs may affect the intestinal vascular barrier function of IBD by regulating mitochondrial stress, ER stress or ER‐mitochondria contact
FIGURE 4
FIGURE 4
S1PRs may regulate vascular function by regulating the source and quantity of eNOS
FIGURE 5
FIGURE 5
S1PR regulators have influences not only on lymphocytes but also on vascular endothelial cells
See this image and copyright information in PMC

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