Mohammed Sabira, Harikumar K B
Cancer Research Program, Rajiv Gandhi Centre for Biotechnology , Thiruvananthapuram , India.
Front Immunol. 2017 Mar 14;8:296. doi: 10.3389/fimmu.2017.00296. eCollection 2017.
Sphingosine 1-phosphate (S1P) is involved in a wide range of cellular processes, which include proliferation, apoptosis, lymphocyte egress, endothelial barrier function, angiogenesis, and inflammation. S1P is produced by two isoenzymes, namely, sphingosine kinase 1 and 2 (SphK1 and 2) and once produced, S1P can act both in an autocrine and paracrine manner. S1P can be dephosphorylated back to sphingosine by two phosphatases (SGPP 1 and 2) or can be irreversibly cleaved by S1P lyase. S1P has a diverse range of functions, which is mediated in a receptor dependent, through G-protein coupled receptors (S1PR1-5) or receptor independent manner, through intracellular targets such as HDACs and TRAF2. The involvement of S1P signaling has been confirmed in various disease conditions including lung diseases. The SphK inhibitors and S1PR modulators are currently under clinical trials for different pathophysiological conditions. There is a significant effort in targeting various components of S1P signaling for several diseases. This review focuses on the ways in which S1P signaling can be therapeutically targeted in lung disorders.
1-磷酸鞘氨醇（S1P）参与广泛的细胞过程，包括增殖、凋亡、淋巴细胞外渗、内皮屏障功能、血管生成和炎症。S1P由两种同工酶产生，即鞘氨醇激酶1和2（SphK1和2），一旦产生，S1P可以以自分泌和旁分泌方式发挥作用。S1P可以被两种磷酸酶（SGPP 1和2）去磷酸化回到鞘氨醇，或者可以被S1P裂解酶不可逆地裂解。S1P具有多种功能，通过G蛋白偶联受体（S1PR1-5）以受体依赖方式介导，或通过细胞内靶点如HDACs和TRAF2以受体非依赖方式介导。S1P信号传导的参与已在包括肺部疾病在内的各种疾病状态中得到证实。SphK抑制剂和S1PR调节剂目前正在针对不同病理生理状况进行临床试验。针对几种疾病的S1P信号传导的各种成分进行靶向治疗正在付出巨大努力。本综述重点关注在肺部疾病中可以靶向S1P信号传导进行治疗的方式。
