title: Membrane-type matrix metalloproteinase 1 regulates trophoblast functions and is reduced in fetal growth restriction.
abstract: Fetal growth restriction (FGR) results from placental insufficiency to adequately supply the fetus. This insufficiency involves impaired cytotrophoblast functions, including reduced migration and invasion, proliferation, and syncytium formation. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a key enzyme in these cellular processes. MT1-MMP exists in various forms: a 63-kDa proenzyme is synthesized as primary translation product, which is cleaved into a 57-kDa membrane-anchored active form. We hypothesized that reduced placental MT1-MMP in FGR impairs trophoblast functions. MT1-MMP mRNA and active enzyme was quantified in placentas from FGR and age-matched control pregnancies. MT1-MMP protein was localized in first-trimester and term placentas. Putative MT1-MMP functions in trophoblasts were determined using two blocking antibodies for measuring migration and proliferation, as well as fusion of primary trophoblasts and trophoblast-derived cells. MT1-MMP was expressed predominantly in the syncytiotrophoblast and the villous and extravillous cytotrophoblasts. In FGR placentas, levels of MT1-MMP mRNA and of active MT1-MMP protein were reduced (-34.2%, P < 0.05, and -21.5%, P < 0.01, respectively), compared with age-matched controls. MT1-MMP-blocking antibodies diminished migration, proliferation, and trophoblast fusion. We conclude that reduced placental MT1-MMP in FGR may contribute to the impaired trophoblast functions associated with this pathology.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria. ursula.hiden@medunigraz.at
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.forename: Nassim
authors.initials: N
authors.lastname: Ghaffari-Tabrizi
authors.forename: Martin
authors.initials: M
authors.lastname: Gauster
authors.forename: Carmen
authors.initials: C
authors.lastname: Tam-Amersdorfer
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
authors.forename: Martina
authors.initials: M
authors.lastname: Dieber-Rotheneder
authors.forename: Uwe
authors.initials: U
authors.lastname: Lang
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*
chemical_list: D019138:Antibodies, Blocking; D015415:Biomarkers; D012333:RNA, Messenger; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14