The role of lysophosphatidic acid receptors in phenotypic modulation of vascular smooth muscle cells |
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Authors: | Zhibin Zhou Jianping Niu Zhijun Zhang |
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Institution: | (1) School of Clinical Medicine, Southeast University, Nanjing, 21009, China;(2) Department of Neurology, The Second Hospital of Xiamen, Xiamen, 361021, China; |
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Abstract: | Lysophosphatidic acid (LPA) is a bioactive lipid with diverse physiological effects via activation of G protein-coupled receptors
(GPCRs). It has been implicated as a specific dedifferentiation factors that can promote phenotypic modulation of cultured
vascular smooth muscle cells (VSMCs) which is critically involved in various vascular disease. However, the role of LPA receptors
and details of their signaling in LPA induced phenotypic modulation are largely unexplored. In this study we detect the expression
of LPA1 and LPA3 in rat aortic smooth muscle cells (RASMCs). LPA promoted RASMCs phenotypic modulation in a dose-dependent
manner and coordinated induced the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated
kinase (ERK). LPA-induced cell phenotypic modulation was significantly inhibited by specific LPA1/LPA3-receptor antagonist
dioctyl-glycerol pyrophosphate (DGPP8:0) at concentration, but this inhibitive effect was lost when the antagonist was coadministered
with a highly selective LPA3 agonist,1-oleoyl-2-Omethyl-rac-glycero-phosphothionate (OMPT). In addition, pertussis toxin (PTX),
a Gi protein inhibitor had little affect on the LPA-induced phenotypic modulation in RASMC. These data suggest that LPA-induced
phenotypic modulation is mediated through the PTX-insensitive G-protein(s), possibly Gq-coupled LPA3 receptor. |
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