title: CNN3 regulates trophoblast invasion and is upregulated by hypoxia in BeWo cells.
abstract: CNN3 is an ubiquitously expressed F-actin binding protein, shown to regulate trophoblast fusion and hence seems to play a role in the placentation process. In this study we demonstrate that CNN3 levels are upregulated under low oxygen conditions in the trophoblast cell line BeWo. Since hypoxia is discussed to be a pro-migratory stimulus for placental cells, we examined if CNN3 is involved in trophoblast invasion. Indeed, when performing a matrigel invasion assay we were able to show that CNN3 promotes BeWo cell invasion. Moreover, CNN3 activates the MAPKs ERK1/2 and p38 in trophoblast cells and interestingly, both kinases are involved in BeWo invasion. However, when we repeated the experiments under hypoxic conditions, CNN3 did neither promote cell invasion nor MAPK activation. These results indicate that CNN3 promotes invasive processes by the stimulation of ERK1/2 and/or p38 under normoxic conditions in BeWo cells, but seems to have different functions at low oxygen levels. We further speculated that CNN3 expression might be altered in human placentas derived from pregnancies complicated by IUGR and preeclampsia, since these placental disorders have been described to go along with impaired trophoblast invasion. Our studies show that, at least in our set of placenta samples, CNN3 expression is neither deregulated in IUGR nor in preeclampsia. In summary, we identified CNN3 as a new pro-invasive protein in trophoblast cells that is induced under low oxygen conditions.
authors: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors: Sarah
authors: S
authors: Appel
authors: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors: Janina
authors: J
authors: Ankerne
authors: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors: Jan
authors: J
authors: Appel
authors: Neonatal and Pediatric Intensive Care Unit, University of Cologne, Children's Hospital, Cologne, Germany.
authors: Andre
authors: A
authors: Oberthuer
authors: Department of Obstetrics and Gynecology, Cologne University, Cologne, Germany.
authors: Peter
authors: P
authors: Mallmann
authors: Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany.
authors: Jörg
authors: J
authors: Dötsch
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; D000096985:Calponins