The role of lysophosphatidic acid in the physiology and pathology of the skin.

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.