title: Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.
abstract: Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.
authors.affiliation: Pharmacy and Biological Science School, Weifang Medical University, Weifang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: School of Public Health, Weifang Medical University, Weifang, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.affiliation: Pharmacy and Biological Science School, Weifang Medical University, Weifang, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Pan
mesh_terms: D001681:Biological Assay; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D015194:Diffusion Chambers, Culture; D004338:Drug Combinations; D005786:Gene Expression Regulation; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008246:Lysophospholipids / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081025:Sphingosine-1-Phosphate Receptors; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C059485:matrigel; C060506:sphingosine 1-phosphate; D003094:Collagen; C482128:MAP2K2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020778:Matrix Metalloproteinase 2; D013110:Sphingosine