Estrogen suppresses expression of the matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) within the mouse uterus.
RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a membrane-anchored glycoprotein which regulates MMP2 and MMP9 activity and has been proposed to play a role in embryo implantation while misexpression of RECK has been associated with a variety of carcinomas. Unfortunately, understanding on the steroidal regulation of uterine RECK is lacking. To address this gap in our knowledge, we examined steroidal regulation and cellular expression of Reck mRNA and protein within the mouse uterus in vivo. Uterine Reck mRNA and protein were decreased by estrogen, while progesterone alone had no effect. The estrogen-induced down regulation could be partially blocked by progesterone. RECK was localized primarily to luminal and glandular epithelial cells and the level of expression was regulated in a similar fashion as in whole tissue by the steroids. Knock-down of endogenous RECK in human endometrial epithelial and stromal cells resulted in a significant increase in active MMP9 expression but not that of pro-MMP9 or MMP2. These studies demonstrate that RECK expression in the mouse uterus is steroidally regulated and that within endometrial epithelial and stromal cells, RECK regulates MMP9, but not MMP2 activity.
Department of Obstetrics and Gynecology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Xuan
X
Zhang
Caitlin
C
Healy
Warren B
WB
Nothnick
D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D004965:Estrogen Antagonists; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; D034741:RNA, Small Interfering; C492025:Reck protein, mouse; D000077267:Fulvestrant; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9