Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation.
Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time- and concentration-dependent manner. Our results indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.
Xia
Yang
Y
Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77030, USA.
Wen
Hong Y
HY
Kellems
Rodney E
RE
D000804:Angiotensin II / Q000494:pharmacology*; D019703:Calcineurin / Q000502:physiology; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014157:Transcription Factors; D000804:Angiotensin II; D016572:Cyclosporine; D019703:Calcineurin; D019808:Losartan