EDG receptors and hepatic pathophysiology of LPA and S1P: EDG-ology of liver injury.
The biological roles of phospholipid growth factors lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been broadly investigated. The cellular effects of LPA and S1P are mediated predominantly via endothelial differentiation gene (EDG) receptors. Yet, the biological significance of LPA, S1P and their EDG receptors in cells of the liver remains unclear. Recent data demonstrate the presence of EDG2 and EDG4 mRNA for LPA receptor in a murine hepatocyte cell line transformed with human TGF-alpha, and in primary mouse hepatocytes. EDG2 receptor protein is expressed in mouse liver, where it appears to be located in nonparenchymal cells. Moreover, we have obtained data suggesting that proliferation of small hepatocyte-progenitors and stem (oval) cells during liver injury is associated with the expression of EDG2 and EDG4 receptors. LPA, and possibly S1P, appear to be essential factors that control proliferation and motility of hepatic stellate cells (HSC) and hepatoma cells. It is proposed that LPA, S1P and their respective EDG receptors play important roles in pathophysiology of chronic liver injury and fibrogenesis. The underlying mechanisms recruited by LPA and S1P in pathogenesis of liver injury remain to be investigated.
Svetlov
Stanislav I
SI
Department of Pathology, University of Florida College of Medicine, 1600 Archer Rd., P.O. Box 100275, Gainesville FL 32610, USA. svetlov@pathology.ufl.edu
Sautin
Yuri Y
YY
Crawford
James M
JM
D000818:Animals; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008099:Liver / Q000293:injuries / Q000503:physiopathology*; D008246:Lysophospholipids / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid
D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid