title: bFGF induces S1P1 receptor expression and functionality in human pulmonary artery smooth muscle cells.
abstract: Sphingosine-1-phosphate (S1P), acting through five closely related G-protein coupled receptors termed S1P1-5, 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 S1P receptor subtypes in human primary pulmonary artery smooth muscle cells (PASMC). We report here that subconfluent PASMC express predominantly S1P2 and S1P3 receptors and we show that S1P1 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 S1P1 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 S1P1 receptor expression and we propose that S1P1 receptor up-regulation could contribute to vascular remodeling.
authors.affiliation: Actelion Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland. magdalena.birker@actelion.com
authors.forename: Magdalena
authors.initials: M
authors.lastname: Birker-Robaczewska
authors.forename: Rolf
authors.initials: R
authors.lastname: Studer
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Haenig
authors.forename: Katalin
authors.initials: K
authors.lastname: Menyhart
authors.forename: Silke
authors.initials: S
authors.lastname: Hofmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Nayler
mesh_terms: D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D049349:Receptors, Lysosphingolipid / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D016222:Fibroblast Growth Factor 2