Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hiden, U; Ghaffari-Tabrizi, N; Gauster, M; Tam-Amersdorfer, C; Cetin, I; Dieber-Rotheneder, M; Lang, U; Desoye, G.
Membrane-type matrix metalloproteinase 1 regulates trophoblast functions and is reduced in fetal growth restriction.
Am J Pathol. 2013; 182(5):1563-1571
Doi: 10.1016/j.ajpath.2013.01.011
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- Führende Autor*innen der Med Uni Graz
- Hiden Ursula
- Co-Autor*innen der Med Uni Graz
- Desoye Gernot
- Dieber-Rotheneder Martina
- Gauster Martin
- Ghaffari Tabrizi-Wizsy Nassim
- Lang Uwe
- Tam-Amersdorfer Carmen
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Antibodies, Blocking - pharmacology
- Biological Markers - metabolism
- Cell Fusion -
- Cell Line -
- Cell Movement - drug effects
- Cell Proliferation - drug effects
- Female -
- Fetal Growth Retardation - enzymology
- Fluorescent Antibody Technique -
- Gene Expression Regulation, Enzymologic - drug effects
- Humans -
- Matrix Metalloproteinase 14 - genetics
- Models, Biological -
- Pregnancy -
- Protein Transport - drug effects
- RNA, Messenger - genetics
- Trophoblasts - drug effects