Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions.
Glial cells missing a (GCMa) belongs to a new transcription factor family. Syncytin was shown to be a target gene of GCMa. Here, we demonstrate that the protein kinase A (PKA) pathway acts upstream of GCMa. After transient transfection of BeWo cells with PKA, GCMa transcriptional activity and both GCMa and syncytin transcripts were upregulated. This increase was accompanied by further cellular differentiation. Using normoxic or hypoxic conditions to mimic pathophysiological settings known to diminish trophoblast differentiation, we found that gene repressive effects of oxygen deficiency were compensated by the induction of the PKA pathway. We propose that GCMa-driven syncytin expression is the key mechanism for syncytiotrophoblast formation.
Knerr
Ina
I
University Hospital for Children and Adolescents, University of Erlangen-Nuremberg, Germany.
Schubert
Steffen W
SW
Wich
Christina
C
Amann
Kerstin
K
Aigner
Thomas
T
Vogler
Tina
T
Jung
Ronny
R
Dötsch
Jörg
J
Rascher
Wolfgang
W
Hashemolhosseini
Said
S
D017209:Apoptosis; D015153:Blotting, Western; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival; D005576:Colforsin / Q000494:pharmacology; D018031:Connexin 43 / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015686:Gene Products, env / Q000378:metabolism / Q000502:physiology*; D005799:Genes, Dominant; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins; D010100:Oxygen / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism*; D015854:Up-Regulation
D018031:Connexin 43; D019925:Cyclin A; D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; D015686:Gene Products, env; D009479:Neuropeptides; D009687:Nuclear Proteins; D011257:Pregnancy Proteins; D014157:Transcription Factors; C405335:syncytin; D005576:Colforsin; D000242:Cyclic AMP; D008156:Luciferases; D017868:Cyclic AMP-Dependent Protein Kinases; D010100:Oxygen