Hendriks-Balk Mariëlle C, Hajji Najat, van Loenen Pieter B, Michel Martin C, Peters Stephan L M, Alewijnse Astrid E
Dept Pharmacology & Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.
Eur J Pharmacol. 2009 Mar 15;606(1-3):25-31. doi: 10.1016/j.ejphar.2009.01.018. Epub 2009 Jan 21.
Regulator of G protein signalling (RGS) protein expression is altered under growth promoting conditions in vascular smooth muscle cells (VSMCs). Since sphingosine-1-phosphate (S1P) is an important growth stimulatory factor, we investigated whether stimulation of VSMCs with S1P results in alterations in mRNA expression levels of several RGS proteins and which signalling components are involved. VSMCs were stimulated with S1P and mRNA expression levels of RGS2, RGS3, RGS4, RGS5 and RGS16 were measured by real-time polymerase chain reaction. S1P caused a time-dependent up-regulation of RGS2 and RGS16 mRNA expression. FTY720-P, a S1P(1)/S1P(3-5) agonist, did not regulate RGS2 mRNA levels although it did up-regulate RGS16 mRNA expression. Pertussis toxin treatment revealed that the S1P-induced RGS16 expression was G(i/o)-dependent whereas up-regulation of RGS2 mRNA was not. Phosphatidylinositol 3-kinase, protein kinase C and mitogen-activated protein kinase kinase apparently were not involved in the S1P-induced up-regulation of both RGS proteins. The present study demonstrates that S1P induces RGS2 and RGS16 mRNA expression but uses distinct S1P receptor subtypes and signalling pathways to regulate expression of these RGS proteins.
G蛋白信号调节因子（RGS）蛋白的表达在血管平滑肌细胞（VSMC）的促生长条件下会发生改变。由于1-磷酸鞘氨醇（S1P）是一种重要的生长刺激因子，我们研究了用S1P刺激VSMC是否会导致几种RGS蛋白的mRNA表达水平发生变化以及涉及哪些信号成分。用S1P刺激VSMC，并通过实时聚合酶链反应测量RGS2、RGS3、RGS4、RGS5和RGS16的mRNA表达水平。S1P引起RGS2和RGS16 mRNA表达的时间依赖性上调。FTY720-P，一种S1P(1)/S1P(3 - 5)激动剂，虽然能上调RGS16 mRNA表达，但不调节RGS2 mRNA水平。百日咳毒素处理表明，S1P诱导的RGS16表达是G(i/o)依赖性的，而RGS2 mRNA的上调则不是。磷脂酰肌醇3激酶、蛋白激酶C和丝裂原活化蛋白激酶激酶显然不参与S1P诱导的这两种RGS蛋白的上调。本研究表明，S1P诱导RGS2和RGS16 mRNA表达，但使用不同的S1P受体亚型和信号通路来调节这些RGS蛋白的表达。
