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.
J Cell Mol Med. 2021 Mar;25(6):2740-2749. doi: 10.1111/jcmm.16333. Epub 2021 Feb 17.
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.
鞘氨醇-1-磷酸受体（S1PRs）通过调节淋巴细胞的迁移和分化对炎症性肠病（IBD）的肠道炎症产生影响。S1PR 调节剂作为一种新兴的治疗方法，正在被研究用于治疗 IBD。然而，S1PRs 在肠道血管中的作用尚未引起太多关注。肠道血管损伤是 IBD 的主要病理生理特征之一，其特征为血管密度增加和屏障功能受损。S1PRs 对血管内皮细胞具有多种效应，包括增殖、迁移、血管生成和屏障稳态。越来越多的证据表明，S1PRs 在 IBD 中异常表达于肠道血管内皮细胞。出乎意料的是，S1PR 调节剂可能会损害肠道血管，例如增加肠道出血；因此，人们认为 S1PRs 参与了 IBD 中肠道血管功能的调节。然而，对于 S1PRs 如何调节肠道血管功能以及参与 IBD 的发生和进展，我们知之甚少。在这篇综述中，我们总结了 S1PRs 在 IBD 中肠道血管损伤中的致病作用及其潜在机制，以便改善包括 S1PR 靶向治疗在内的 IBD 治疗实践。
