title: Extracellular matrix metalloproteinase inducer regulates metalloproteinases in human uterine endometrium.
abstract: BACKGROUND
  Endometrial remodeling occurs during each menstrual cycle in women and also during the establishment of endometriosis. Both processes involve the production of metalloproteinases (MMPs) by uterine endometrial cells.
  
  
  OBJECTIVE
  The objective of this study was to determine whether tissue remodeling and endometrial invasion involve activation of MMPs by extracellular matrix metalloproteinase inducer (EMMPRIN).
  
  
  METHODS
  EMMPRIN expression was examined by immunohistochemistry and real-time PCR in ectopic and eutopic endometria. For functional assays, human uterine fibroblasts were treated in the absence or presence of IL-1beta (10 ng/ml) or purified native EMMPRIN (0.5 or 1 microg/ml) for 24 h. Cellular RNA and conditioned medium were assayed by real-time PCR or immunoblotting.
  
  
  RESULTS
  EMMPRIN protein localized to epithelial and fibroblast cells of eutopic and ectopic endometria. The pattern of localization was regulated by ovarian hormones. EMMPRIN mRNA levels varied throughout the menstrual cycle in parallel with the cyclic changes in estradiol. EMMPRIN treatment (0.5 microg/ml) of human uterine fibroblast cells stimulated MMP-1 (5.23-fold) and MMP-2 (8.55-fold), but not MMP-3, mRNA levels over levels in control cells (P < 0.05). EMMPRIN treatment (1 microg/ml) stimulated endogenous EMMPRIN (1.6-fold) mRNA levels (P > 0.05). IL-1beta stimulated MMP-1 (5.6-fold), MMP-2 (2.8-fold), and MMP-3 (75-fold) gene expression, but not EMMPRIN, over levels in control cells (P < 0.05). Both EMMPRIN and IL-1beta treatments stimulated MMP-1, -2, and -3, but not EMMPRIN protein secretion, with 0.5 microg/ml producing the greatest response.
  
  
  CONCLUSIONS
  The ability of EMMPRIN to stimulate MMP secretion by endometrial fibroblasts indicates its potential role in uterine remodeling and the pathogenesis of endometriosis.
authors.affiliation: University of Illinois, 1207 West Gregory Drive, Urbana, Illinois 61801, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Braundmeier
authors.forename: A T
authors.initials: AT
authors.lastname: Fazleabas
authors.forename: B A
authors.initials: BA
authors.lastname: Lessey
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: B P
authors.initials: BP
authors.lastname: Toole
authors.forename: R A
authors.initials: RA
authors.lastname: Nowak
mesh_terms: D051926:Basigin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004715:Endometriosis / Q000209:etiology; D004717:Endometrium / Q000201:enzymology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D051926:Basigin; D045726:Metalloproteases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1