Ovarian cancer G protein-coupled receptor 1-dependent and -independent vascular actions to acidic pH in human aortic smooth muscle cells

American Journal of Physiology. Heart and Circulatory Physiology
Jin-Peng LiuFumikazu Okajima

Abstract

Atherosclerosis is a chronic inflammation disease characterized by acidic micromilieu and the accumulation of numerous bioactive lipid mediators, such as lysophosphatidic acid (LPA) and prostaglandins, in the atherosclerotic lesion. Chronic acidification induced various effects on vascular smooth muscle cells, but the molecular mechanisms underlying these effects remain unknown. In this study, we examine the role of proton-sensing ovarian cancer G protein-coupled receptor 1 (OGR1) in extracellular acidification-induced regulation of cyclooxygenase (COX)-2 induction, PGI(2) production, MAPK phosphatase (MKP)-1 expression, and plasminogen activator inhibitor (PAI)-1 expression and proliferation in human aortic smooth muscle cells (AoSMCs). Experiments with knockdown with small interfering RNA specific to OGR1 and specific inhibitors for G proteins showed that acidification-induced COX-2 expression, PGI(2) production, and MKP-1 expression, but not PAI-1 expression and inhibition of proliferation, were dependent on OGR1 and mainly mediated by G(q/11) protein. LPA remarkably enhanced, through the LPA(1) receptor/G(i) protein, the OGR1-mediated vascular actions to acidic pH. In conclusion, acidic pH-induced vascular actions of AoSMCs...Continue Reading

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Citations

Nov 15, 2011·Archives of Pharmacal Research·Sun Young ParkUy Dong Sohn
Jan 13, 2015·Biochemical and Biophysical Research Communications·Yuta MochimaruHideaki Tomura
Jun 9, 2015·Journal of Receptor and Signal Transduction Research·Rie Abe-OhyaFutoshi Nara
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Apr 23, 2020·Animal Models and Experimental Medicine·Wenlong ZhangRan Gao
Feb 7, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ajay P NayakRaymond B Penn

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