Disclosure: All the authors have nothing to declare.
Original Research Article
Version of Record online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 1821–1828, May 2012
How to Cite
Ciarmela, P., Marzioni, D., Islam, Md. S., Gray, P. C., Terracciano, L., Lorenzi, T., Todros, T., Petraglia, F. and Castellucci, M. (2012), Possible role of RKIP in cytotrophoblast migration: immunohistochemical and in vitro studies. J. Cell. Physiol., 227: 1821–1828. doi: 10.1002/jcp.22907
This study is dedicated to Peter Kaufmann (Aachen, Germany), dear friend, teacher, and outstanding scientist, in memory of his fundamental contributions to the present understanding of the human placenta.
- Issue online: 23 JAN 2012
- Version of Record online: 23 JAN 2012
- Accepted manuscript online: 5 JUL 2011 10:29AM EST
- Manuscript Accepted: 16 JUN 2011
- Manuscript Received: 8 MAR 2011
- Italian Ministry of the University and Research. Grant Number: PRIN 2008
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. J. Cell. Physiol. 227: 1821–1828, 2012. © 2011 Wiley Periodicals, Inc.