溶血磷脂酸在皮肤生理和病理中的作用。
The role of lysophosphatidic acid in the physiology and pathology of the skin.
机构信息
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha 410008, China.
出版信息
Life Sci. 2019 Mar 1;220:194-200. doi: 10.1016/j.lfs.2018.12.040. Epub 2018 Dec 22.
Lysophosphatidic acid (LPA) is the simplest phospholipid found in nature. LPA is mainly biosynthesized in tissues and cells by autotoxin and PA-PLA1α/PA-PLA1β and is degraded by lipid phosphate phosphatases (LPPs). It is an important component of biofilm, an extracellular signal transmitter and intracellular second messenger. After targeting to endothelial differentiation gene (Edg) family LPA receptors (LPA1, LPA2, LPA3) and non-Edg family LPA receptors (LPA4, LPA5, LPA6), LPA mediates physiological and pathological processes such as embryonic development, angiogenesis, tumor progression, fibrogenesis, wound healing, ischemia/reperfusion injury, and inflammatory reactions. These processes are induced through signaling pathways including mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3K)/Akt, protein kinase C (PKC)-GSK3β-β-catenin, Rho, Stat, and hypoxia-inducible factor 1-alpha (HIF-1α). LPA is involved in multiple physiological and pathological processes in the skin. It not only regulates skin function but also plays an important role in hair follicle development, skin wound healing, pruritus, skin tumors, and scleroderma. Pharmacological inhibition of LPA synthesis or antagonization of LPA receptors is a new strategy for the treatment of various skin disorders. This review focuses on the current understanding of the pathophysiologic role of LPA in the skin.
溶血磷脂酸（LPA）是自然界中最简单的磷脂。LPA 主要由自毒素和 PA-PLA1α/PA-PLA1β在组织和细胞中生物合成，并被脂质磷酸酶（LPPs）降解。它是生物膜的重要组成部分，是一种细胞外信号转导物和细胞内第二信使。LPA 靶向内皮分化基因（Edg）家族 LPA 受体（LPA1、LPA2、LPA3）和非 Edg 家族 LPA 受体（LPA4、LPA5、LPA6）后，介导胚胎发育、血管生成、肿瘤进展、纤维化、伤口愈合、缺血/再灌注损伤和炎症反应等生理和病理过程。这些过程通过丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3-激酶（PI3K）/Akt、蛋白激酶 C（PKC）-GSK3β-β-连环蛋白、Rho、Stat 和缺氧诱导因子 1-α（HIF-1α）等信号通路诱导。LPA 参与皮肤的多种生理和病理过程。它不仅调节皮肤功能，而且在毛囊发育、皮肤伤口愈合、瘙痒、皮肤肿瘤和硬皮病中发挥重要作用。抑制 LPA 合成或拮抗 LPA 受体是治疗各种皮肤疾病的新策略。本文综述了目前对 LPA 在皮肤中的生理病理作用的认识。
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