Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro.
Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal growth-promoting properties. However, our understanding of the factors that regulate OECs is at early stages. Lysophosphatidic acid (LPA) is a lipid that influences diverse functions in the nervous system. Recent studies suggest that glial cells, including astrocytes and Schwann cells, are important targets of LPA. However, the influences of LPA on OECs are not known. To address if LPA can influence OECs, we examined effects of LPA on the proliferation and migration of OECs and intracellular effector events. Initially, we observed that OECs expressed the genes for LPA1, LPA2, and LPA3 receptors. When OECs were treated with LPA, we observed stimulated proliferation and migration of OECs. Treatment of OECs with LPA also induced actin cytoskeleton reorganization and focal adhesion assembly. These effects of LPA were blocked by treatment with C3 exoenzyme or Y-27632, which inhibit Rho-GTPase and Rho-associated kinase, respectively. Effects of LPA on OEC proliferation were blocked by the MEK inhibitors PD098059 and U0126 and by the phosphotidylinositol 3-kinase (PI 3-K) inhibitors LY0294002 and wortmannin. These results show that LPA acts via Rho-GTPase, MAPK, and PI 3-K signaling cascades to influence OEC proliferation, migration, and cytoskeleton assembly.
Yan
Henglin
H
Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Lu
Dongchen
D
Rivkees
Scott A
SA
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D020741:rho GTP-Binding Proteins