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

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.

Sphingosine‐1‐Phosphate Receptor Targeted PLGA Nanobubbles for Inflammatory Vascular Endothelial Cell Catching

“…[ 17 ] Studies have shown that S1PR1 expression changes dynamically when endothelial cells are activated, injured, or inflamed. [ 18 ] Therefore, the mechanism underlying the rapid and excellent targeting effect of the S1P@CD‐PLGA NBs on inflammatory vascular endothelial cells was further studied. First, according to the Western blot qualitative results in Figure a and quantitative results in Figure 5b of S1PR1 protein expression in both normal rat carotid endothelial cells and histamine‐induced inflammatory rat carotid endothelial cells, it was found that histamine‐induced inflammatory vascular endothelial cells expressed more S1PR1 than normal endothelial cells, which showed a 1.35‐fold enhancement in S1PR1 level ( p = 0.0079).…”

Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）

“…Furthermore, increased VEGF levels and MPO activity were noted in the colonic tissues of DSS-treated mice. Elevated VEGF expression has been linked directly to pathological angiogenesis and inflammation in both human and experimental colitis [ [ 34 ]]. Rutin markedly downregulated VEGF expression levels and MPO activity, suggesting its potential role in protecting vascular endothelial barrier function.…”

Characterization of Bovine Intraepithelial T Lymphocytes in the Gut

“…CD62L is essential for T cell adhesion, facilitating lymphocyte homing to secondary lymphatic organs. In contrast, CD69 serves a dual role: it counters the sphingosine-1-phosphate receptor, which typically signals to T cells to move into the bloodstream, and acts as a T cell activation marker [ 149 , 150 , 187 , 188 , 189 ]. Bovine T-IELs express low levels of CD62L and high levels of CD69, a pattern also observed in humans and mice [ 61 , 190 ].…”