title: Receptor-mediated vascular smooth muscle migration induced by LPA involves p38 mitogen-activated protein kinase pathway activation.
abstract: Lysophosphatidic acid (LPA), a naturally occurring glycerophospholipid, can evoke various biological responses, including cell migration, proliferation and survival, via activation of G protein-coupled receptors (GPCRs). However, the role of LPA receptors and details of LPA signaling in migration are largely unexplored. In this study we detect the expression of LPA1 and LPA3 receptors in rat aortic smooth muscle cells (RASMCs). LPA stimulated RASMCs migration in a dose-dependent manner and induced the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK). LPA-induced cell migration was significantly inhibited by specific LPA1/LPA3-receptor antagonist Dioctylglycerol pyrophosphate (8:0) (DGPP8.0) at higher concentration. Migration of cells toward LPA was partially, but significantly, reduced in the presence of SB-203580, a p38 MAPK inhibitor, but not PD98059, an ERK inhibitor. In addition, pertussis toxin (PTX), a Gi protein inhibitor, induced an inhibitory effect on p38 MAPK, ERK phosphorylation and RASMCs migration. These data suggest that LPA-induced migration is mediated through the Gi-protein-coupled LPA1 receptor involving activation of a PTX-sensitive Gi / p38MAPK pathway.
authors.affiliation: School of Clinical Medicine, Southeast University, Nanjing 21009, China.|Department of Neurology, The second Hospital of Xiamen, Xiamen 361021, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The second Hospital of Xiamen, Xiamen 361021, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Niu
authors.affiliation: School of Clinical Medicine, Southeast University, Nanjing 21009, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D011756:Diphosphates / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D005419:Flavonoids; D007093:Imidazoles; D008246:Lysophospholipids; D011725:Pyridines; D049368:Receptors, Lysophosphatidic Acid; C408642:diacylglycerol pyrophosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D005990:Glycerol; C032881:lysophosphatidic acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one