1-磷酸鞘氨醇及其信号通路在炎症相关性疾病中的作用

Role of sphingosine-1-phosphate and its signaling pathway in inflammation-related diseases

1-磷酸鞘氨醇(sphingosine 1-phosphate,S1P)是细胞膜鞘磷脂在代谢过程中产生的一类重要的信号分子,S1P可被转运到细胞外,通过作用于S1P受体,激活一系列下游信号分子发挥作用,如Ras/Raf/ERK、PI3K/Akt等,也可作为第二信使直接作用于细胞内靶点,如HDAC、TRAF2。其介导的信号通路在很多生理和病理过程中发挥作用,如细胞增殖和迁移、炎性细胞因子浸润、血管生成、自身免疫等。该文分别从S1P的胞外及胞内两种作用方式,探讨S1P及其信号通路在炎症相关性疾病中的作用,综述S1P信号通路相关药物研究进展。

Sphingosine 1-phosphate(S1P) is an important signal molecule produced by the metabolism of cell membrane sphingomyelin.S1P can be transported to the extracellular domain,and plays a role in activating a series of downstream signals,such as Ras/Raf/ERK,PI3K/AKT,by acting on S1P receptors.It can also act as a second messenger directly on intracellular targets such as HDAC,TRAF2.Its mediated signaling pathway plays a role in many physiological and pathological processes such as cell proliferation and migration,inflammatory cytokine infiltration,angiogenesis and autoimmunity.This article explores the role of S1P and its signaling pathways in inflammation-related diseases from the extracellular and intracellular roles of S1P,and reviews the research progress of S1P signaling pathway related drugs.