Role of Lysophosphatidic Acid in Vascular Smooth Muscle Cell Proliferation.

Role of Lysophosphatidic Acid in Vascular Smooth Muscle Cell Proliferation. Can J Physiol Pharmacol. 2019 Aug 01;: Authors: Liu Y, Chen F, Ji L, Zhang L, Xu YJ, Dhalla NS Abstract Lysophosphatidic acid (LPA) is an important lipid molecule for signal transduction in cell proliferation. Although the effects of LPA on vascular smooth muscle (VSM) cell growth have been reported previously, the underlying mechanisms of its action are not fully understood. The present study was undertaken to investigate the effects of some inhibitors of different protein kinases and other molecular targets on LPA-induced DNA synthesis as well as gene expression in the aortic VSM cells. The DNA synthesis was studied by [3H]-thymidine incorporation method and the gene expression was investigated by real time PCR technique. It was observed that the LPA-induced DNA synthesis was attenuated by inhibitors of protein kinase C (PKC; staurosporine, calphostin C and bisindolylmaleimide), phosphoinositide 3-kinase (PI3K; wortmannin, and LY294002), and ribosomal p70S6 kinase (p70S6K; rapamycin). The inhibitors of guanine protein coupled receptors (GPCR; pertussis toxin), phospholipase C (PLC; U73122 and D609), and sodium-hydrogen exchanger (NHE; amiloride and dimethyl amiloride) were also shown to depress the LPA-induced DNA synthesis. Furthermore, gene expressions for PLC β1 isoform, PKC δ and ε isoforms, casein kinase II β isoform and endothelin-1A receptors wer...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research