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.
Highlights
Lysophosphatidic acid (LPA) is a member of the lysophospholipid class of phospholipids that is an intermediate in phospholipid metabolism [1]
LPA1 is the receptor with the widest distribution, the expression of LPA2 and LPA3 is somewhat more restricted, whereas LPA4 is expressed only in the ovary [24], LPA5 is mainly expressed in the lymphocyte compartment of the gastrointestinal tract, sensory dorsal root ganglia as well as embryonic stem cells [25,26], LPA6 was expressed in placenta, ovary, testis, prostate, brain, and skeletal muscle [27]
We demonstrate that rat aortic smooth muscle cells (RASMCs) expressed two types of LPA receptor transcripts (LPA1 and LPA3) (Figure 2), and LPA-induced migration in RASMCs is mediated by specific LPA
Summary
Lysophosphatidic acid (LPA) is a member of the lysophospholipid class of phospholipids that is an intermediate in phospholipid metabolism [1]. LPA elicits these cellular effects on most cell types through the activation of its specific G protein–coupled receptors (GPCRs). When an agonist interacts with a specific GPCR, its associated G-protein is activated and induces a specific intracellular pathway that leads to the final cellular response. SMCs exhibit enhanced migration in response to upregulation of the LPA3 receptor [33].Damirin A et al [34] demonstrated that LPA1 receptors are involved in the LDL-induced migration of human coronary artery smooth muscle cells. The roles of LPA receptors in LPA-stimulated VSMCs migration are far from been elucidated in detail. The present study was designed to determine the involvement of LPA receptors in LPA-stimulated migration of VSMC and the signaling pathways involved
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