Annual Review of Pathology: Mechanisms of Disease ( IF 28.4 ) Pub Date : 2022-01-24 , DOI: 10.1146/annurev-pathol-050420-025929 Kuniyuki Kano 1, 2 , Junken Aoki 1, 2 , Timothy Hla 3, 4
Lysophospholipids, exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are produced by the metabolism and perturbation of biological membranes. Both molecules are established extracellular lipid mediators that signal via specific G protein–coupled receptors in vertebrates. This widespread signaling axis regulates the development, physiological functions, and pathological processes of all organ systems. Indeed, recent research into LPA and S1P has revealed their important roles in cellular stress signaling, inflammation, resolution, and host defense responses. In this review, we focus on how LPA regulates fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and disorders of neuroectodermal development such as hydrocephalus and alopecia. In addition, we discuss how S1P controls collective behavior, apoptotic cell clearance, and immunosurveillance of cancers. Advances in lysophospholipid research have led to new therapeutics in autoimmune diseases, with many more in earlier stages of development for a wide variety of diseases, such as fibrotic disorders, vascular diseases, and cancer.
中文翻译:
健康和疾病中的溶血磷脂介质
以溶血磷脂酸 (LPA) 和鞘氨醇 1-磷酸 (S1P) 为例的溶血磷脂是由生物膜的代谢和扰动产生的。这两种分子都是已建立的细胞外脂质介质,可通过脊椎动物中的特定 G 蛋白偶联受体发出信号。这个分布广泛的信号轴调节所有器官系统的发育、生理功能和病理过程。事实上,最近对 LPA 和 S1P 的研究揭示了它们在细胞应激信号、炎症、消退和宿主防御反应中的重要作用。在这篇综述中,我们重点关注 LPA 如何调节纤维化、神经性疼痛、异常血管生成、子宫内膜异位症和神经外胚层发育障碍(如脑积水和脱发)。此外,我们讨论 S1P 如何控制集体行为,凋亡细胞清除和癌症的免疫监视。溶血磷脂研究的进展催生了自身免疫性疾病的新疗法,还有更多疗法处于早期开发阶段,可用于多种疾病,例如纤维化疾病、血管疾病和癌症。