title: Polarized release of matrix metalloproteinase-2 and -9 from cultured human placental syncytiotrophoblasts.
abstract: The large increase in placental surface area and fetal villous vascular development in the third trimester of pregnancy requires degradation and reformation of the placental basal lamina. Degradation is carried out by matrix metalloproteinases (MMPs) secreted by adjacent cells. Although the gelatinases, MMP-2 and MMP-9, which are released by extravillous cytotrophoblasts (CTs) are believed to play crucial roles in early placental expansion, neither has been reported in third trimester villous trophoblasts nor has appropriate (basolateral) release of any MMP by the highly polarized syncytiotrophoblast (ST) been demonstrated. We demonstrated villous trophoblast expression of both MMP-2 and MMP-9 by in situ immunohistochemistry and by Western blot analysis and zymography of lysates and culture supernatants of highly purified villous CTs. We also found that epidermal growth factor (EGF)-stimulated CT differentiation into ST and stimulation by the phorbol diester, PMA, both increase MMP-9 secretion. The direction of MMP release was determined with confluent cultures of ST on porous membranes. We found that >90% of MMP-2 and MMP-9 were released from the basolateral surface. We conclude that villous STs express and release gelatinases from their basolateral surfaces in a regulated manner and suggest that such polarized release may be important to villous tissue remodeling.
authors.affiliation: Departments of Pharmacology, Obstetrics and Gynaecology, Microbiology and Immunology, and Perinatal Research Centre, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Sawicki
authors.forename: M W
authors.initials: MW
authors.lastname: Radomski
authors.forename: B
authors.initials: B
authors.lastname: Winkler-Lowen
authors.forename: A
authors.initials: A
authors.lastname: Krzymien
authors.forename: L J
authors.initials: LJ
authors.lastname: Guilbert
mesh_terms: D015153:Blotting, Western; D002469:Cell Separation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000378:metabolism; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology*
chemical_list: D007074:Immunoglobulin G; D010703:Phorbol Esters; D004815:Epidermal Growth Factor; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9