AQP1 gene expression is upregulated by arginine vasopressin and cyclic AMP agonists in trophoblast cells.
Aquaporins (AQPs) are water channels that regulate water flow in many tissues. As AQP1 is a candidate to regulate placental fluid exchange, we sought to investigate the effect of arginine vasopressin (AVP) and cAMP agonists on AQP1 gene expression in first trimester-derived extravillous cytotrophoblasts (HTR-8/Svneo) and two highly proliferative carcinoma trophoblast-like cell lines but with a number of functional features of the syncytiotrophoblast namely; JAR and JEG-3 cells. Our data demonstrated that AVP (0.1 nM) significantly increased the expression of AQP1 mRNA at 10 h in HTR-8/SVneo and JEG-3 cells (P<0.05). Both SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP, and forskolin, an adenylate cyclase stimulator significantly increased AQP1 mRNA expression in all cell lines after 2 h in a dose-dependent manner (P<0.05) with a parallel increase in protein expression. In the time course study, 5 microM of either SP-cAMP or forskolin significantly stimulated AQP1 mRNA expression after 2 h in HTR-8/SVneo cells and after 10 h in JAR and JEG-3 cells. AQP1 protein expression was highest after 20 h in both HTR-8/SVneo and JEG-3 cells (P<0.05). AVP-stimulated cAMP elevation was blocked in the presence of 9-(tetrahydro-2'-furyl) adenine (SQ22536) (100 microM), a cell-permeable adenylate cyclase inhibitor (P<0.05). These results indicate that in trophoblasts-like cells AQP1 gene expression is upregulated by both AVP and cAMP agonists. Furthermore, our data demonstrate that a cAMP-dependent pathway is responsible for the AVP effect on AQP1. Thus, modulation of AQP1 expression by maternal hormones may regulate invasion and fetal-placental-amnion water homeostasis during gestation.
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine, University of California, Los Angeles, CA 90502, USA. lbelkacemi@obgyn.humc.edu
Louiza
L
Belkacemi
Marie H
MH
Beall
Thomas R
TR
Magee
Margaret
M
Pourtemour
Michael G
MG
Ross
D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013873:Thionucleotides / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D013873:Thionucleotides; D001127:Arginine Vasopressin; D051398:Aquaporin 1; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP