Bioactive lysophospholipids and mesangial cell intracellular signaling pathways: role in the pathobiology of kidney disease.

Lysophosphatidic acid (LPA), lyso-phosphatidylcholine (LPC), and sphingosine-1-phosphate (S1P) are major biologically active lysophospholipids (LPLs) that are produced by activated platelets, monocyte/macrophages, and many types of mammalian cells. LPLs have been shown to induce a wide array of physiological and pathophysiological properties including cellular differentiation, proliferation, migration, extracellular matrix deposition, change in morphology, and chemotactic responses. The recent cloning and identification of G protein-coupled receptors as specific receptors for LPLs created a great deal of interest in LPLs signaling and diverse biological responses. The pathobiological role of LPLs has been implicated in a number of pathological states and human diseases including atherosclerosis, glomerulosclerosis, post-ischemic renal failure, polycystic kidney disease, and ovarian cancer. Although the research in this area is growing at an enormous rate, this review is specifically focused on the recent understanding of the pathophysiological properties of LPA and LPC with special reference to kidney diseases, and their specific G-protein-coupled receptors and intracellular signaling pathways.