bFGF Induces S1P1 Receptor Expression and Functionality in Human Pulmonary Artery Smooth Muscle Cells

Sphingosine-1-phosphate (S1P), acting through five closely related G-protein coupled receptors termed S1P(1-5), has recently emerged as a possible regulator of smooth muscle cell (SMC) physiology with the potential to induce contraction, proliferation and stress fiber formation. In the present study, real-time quantitative PCR was used to determine the expression patterns of SIP receptor subtypes in human primary pulmonary artery smooth muscle cells (PASMC). We report here that subconfluent PASNIC express predominantly S1P(2) and S1P(3) receptors and we show that SIP, receptor mRNA levels are significantly up-regulated following basic fibroblast growth factor (bFGF) treatment. As a consequence, increased responsiveness, as measured by impedance and ERK1/2 phosphorylation, was observed upon stimulation with a specific S I P 1 receptor agonist SEW2871. We therefore demonstrate, for the first time, that a growth factor that was previously shown to be involved in physiological and pathological changes of SMC function induced S I P I receptor expression and we propose that S I P 1 receptor up-regulation could contribute to vascular remodeling. J. Cell. Biochem. 105: 1139-1145, 2008. (c) 2008 Wiley-Liss, Inc.