title: Possible role of RKIP in cytotrophoblast migration: immunohistochemical and in vitro studies.
abstract: Raf kinase inhibitor protein (RKIP) regulates growth and differentiation signaling of mitogen-activated protein kinases (MAPK), GRK2 and NF-kappaB pathways each of which regulates cytotrophoblast differentiation and normal placental development. We show here that RKIP is expressed in human normal and preeclampic placentas as detected by immunostaining. RKIP was detected in villous cytotrophoblast in normal placenta and switched to syncytiotrophoblast in pre-eclampsia (PE)-complicated pregnancies. RKIP was also localized in extravillous cytotrophoblast of cell islands and cell columns both in normal and in PE placentas, although staining was less uniform in the latter specimens. In order to test RKIP involvement in cytotrophoblast function, we performed in vitro studies on HTR-8/SVneo cells, a first trimester cytotrophoblast cell line. We show that the RKIP inhibitor locostatin reduces ERK phosphorylation and impairs HTR-8/SV neo cells motility in wound closure experiments. We also document the presence of GRK2 mRNA, the reduction of phosphorylated RKIP expression by locostatin and the induction of PAI mRNA expression in HTR-8/SV neo cells, suggesting the involvement of GRK2 and NF-kappaB pathways in these cells. In conclusion, our work provides evidence that RKIP is a novel factor expressed in cytotrophoblast cells where it likely regulates cell migration.
authors: Faculty of Medicine, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy. p.ciarmela@univpm.it
authors: Pasquapina
authors: P
authors: Ciarmela
authors: Daniela
authors: D
authors: Marzioni
authors: Md Soriful
authors: MS
authors: Islam
authors: Peter Clarke
authors: PC
authors: Gray
authors: Luigi
authors: L
authors: Terracciano
authors: Teresa
authors: T
authors: Lorenzi
authors: Tullia
authors: T
authors: Todros
authors: Felice
authors: F
authors: Petraglia
authors: Mario
authors: M
authors: Castellucci
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D023303:Oxazolidinones / Q000494:pharmacology; D049488:Phosphatidylethanolamine Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D023303:Oxazolidinones; D049488:Phosphatidylethanolamine Binding Protein; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C529490:locostatin; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D020928:Mitogen-Activated Protein Kinases