Regulation of plasminogen activator in rat endometrial stromal cells: the role of prostaglandin E2.
The rat endometrium undergoes decidualization, a tissue remodeling process, during embryo implantation. Plasminogen activator (PA), particularly the urokinase-type PA (uPA), has been implicated in tissue remodeling. The present study determined whether rat endometrial stromal cells secrete uPA during decidualization in vitro and, if so, whether the secretion is regulated by prostaglandins that are required in decidualization. Endometrial stromal cells were obtained from rats that had been treated with estrogen and progesterone to sensitize their uteri for decidualization, and the cells were cultured for up to 72 h in a serum-free medium. PA activity in the conditioned medium, as determined by a chromogenic assay, increased steadily during the 72-h culture period. PA secretion decreased when endogenous prostaglandin synthesis was inhibited by the addition of indomethacin to the cell cultures. The inhibitory effect of indomethacin on PA secretion was reversed by prostaglandin E2, and much less effectively by prostaglandin F2 alpha. PA activity in the medium was due primarily to uPA because 1) PA activity was inhibited by a uPA-specific inhibitor-amiloride-and by an anti-mouse uPA antibody, and 2) the predominant PA activity in the medium, as identified in zymography, had a molecular mass of approximately 40 kDa, similar to that reported for uPA. Northern blot analyses of RNA from the cultured cells demonstrated that the steady-state levels of mRNA for uPA, but not for tPA and plasminogen activator inhibitor-1, were decreased by indomethacin; this decrease was reversed by prostaglandin E2. Taken together, the data indicate that rat endometrial stromal cells secrete uPA during decidualization in vitro, and that prostaglandin E2 regulates uPA secretion by the decidualizing cells by directly increasing uPA gene transcription and/or stabilizing its transcripts. These findings may help to partially elucidate the mechanism of action of prostaglandin E2 in decidualization.
Zhang
X
X
Department of Obstetrics and Gynaecology, University of Calgary, Alberta, Canada. xzhang@acs.ucalgary.ca
Shu
M A
MA
Ross
H E
HE
Kennedy
T G
TG
D000818:Animals; D015152:Blotting, Northern; D017077:Culture Media, Conditioned; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; D010712:Phosphatidic Acids; D012333:RNA, Messenger; D015237:Dinoprost; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone; D007213:Indomethacin