CONTEXT: Preeclampsia is a pregnancy-specific disorder that features insufficient extravillous trophoblast (EVT) invasion. We have previously shown that MUC1 expression in human placenta increases with gestational age and inhibits choriocarcinoma cell invasion. OBJECTIVE: Here, we studied whether MUC1 expression in preeclamptic placentas is dysregulated and the mechanism of EVT invasion regulated by MUC1. DESIGN: MUC1 expression in severe preeclamptic placentas and gestational age-matched control placentas was analyzed by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The effects of MUC1 expression on cell-matrix adhesion, invasion, and cell signaling were studied in HTR8/SVneo EVT cells. RESULTS: We found that MUC1 mRNA and MUC1 protein were significantly up-regulated in severe preeclamptic placentas when compared with the gestational age-matched control placentas. Immunohistochemical analyses showed increased expression of MUC1 in the syncytiotrophoblast and EVT of severe preeclamptic placentas. In addition, MUC1 overexpression suppressed cell-matrix adhesion and invasion of EVT cells. Importantly, our data showed that MUC1 overexpression inhibited β1-integrin activity and phosphorylation of focal adhesion kinase, whereas the surface expression of β1-integrin was not significantly changed. CONCLUSIONS: Our findings suggest that MUC1 is overexpressed in severe preeclamptic placentas and that MUC1 overexpression suppresses EVT invasion mainly via modulating β1-integrin signaling.
CONTEXT: Preeclampsia is a pregnancy-specific disorder that features insufficient extravillous trophoblast (EVT) invasion. We have previously shown that MUC1 expression in human placenta increases with gestational age and inhibits choriocarcinoma cell invasion. OBJECTIVE: Here, we studied whether MUC1 expression in preeclamptic placentas is dysregulated and the mechanism of EVT invasion regulated by MUC1. DESIGN:MUC1 expression in severe preeclamptic placentas and gestational age-matched control placentas was analyzed by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The effects of MUC1 expression on cell-matrix adhesion, invasion, and cell signaling were studied in HTR8/SVneo EVT cells. RESULTS: We found that MUC1 mRNA and MUC1 protein were significantly up-regulated in severe preeclamptic placentas when compared with the gestational age-matched control placentas. Immunohistochemical analyses showed increased expression of MUC1 in the syncytiotrophoblast and EVT of severe preeclamptic placentas. In addition, MUC1 overexpression suppressed cell-matrix adhesion and invasion of EVT cells. Importantly, our data showed that MUC1 overexpression inhibited β1-integrin activity and phosphorylation of focal adhesion kinase, whereas the surface expression of β1-integrin was not significantly changed. CONCLUSIONS: Our findings suggest that MUC1 is overexpressed in severe preeclamptic placentas and that MUC1 overexpression suppresses EVT invasion mainly via modulating β1-integrin signaling.
Authors: Issaka Yougbaré; Wei-She Tai; Darko Zdravic; Brigitta Elaine Oswald; Sean Lang; Guangheng Zhu; Howard Leong-Poi; Dawei Qu; Lisa Yu; Caroline Dunk; Jianhong Zhang; John G Sled; Stephen J Lye; Jelena Brkić; Chun Peng; Petter Höglund; B Anne Croy; S Lee Adamson; Xiao-Yan Wen; Duncan J Stewart; John Freedman; Heyu Ni Journal: Nat Commun Date: 2017-08-09 Impact factor: 14.919
Authors: Nadine Segond; Séverine A Degrelle; Sarah Berndt; Elodie Clouqueur; Christine Rouault; Bruno Saubamea; Philippe Dessen; Keith S K Fong; Katalin Csiszar; Josette Badet; Danièle Evain-Brion; Thierry Fournier Journal: PLoS One Date: 2013-11-12 Impact factor: 3.240