Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hiden, U; Lassance, L; Tabrizi, NG; Miedl, H; Tam-Amersdorfer, C; Cetin, I; Lang, U; Desoye, G.
Fetal Insulin and IGF-II Contribute to Gestational Diabetes Mellitus (GDM)-Associated Up-Regulation of Membrane-Type Matrix Metalloproteinase 1 (MT1-MMP) in the Human Feto-Placental Endothelium.
J Clin Endocrinol Metab. 2012; 97(10): 3613-3621.
Doi: 10.1210/jc.2012-1212
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- Führende Autor*innen der Med Uni Graz
- Hiden Ursula
- Co-Autor*innen der Med Uni Graz
- Desoye Gernot
- Ghaffari Tabrizi-Wizsy Nassim
- Lang Uwe
- Miedl Heidi
- Tam-Amersdorfer Carmen
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- Abstract:
- Context: Gestational diabetes mellitus (GDM)-associated hormonal and metabolic derangements in mother and fetus affect placental development and function. Indeed, in GDM, placentas are characterized by hypervascularization and vascular dysfunction. The membrane-type matrix metalloproteinase 1 (MT1-MMP) is a key player in angiogenesis and vascular expansion. Objective: Here, we hypothesized elevated placental MT1-MMP levels in GDM induced by components of the diabetic environment. Therefore, we measured placental MT1-MMP in normal vs. GDM pregnancies, identified potential functional consequences, and investigated the contribution of hyperglycemia and the insulin/IGF axis. Design: Immunohistochemistry identified placental cell types expressing MT1-MMP. MT1-MMP was compared between normal and GDM placentas by immunoblotting. Quantitative PCR of MT1-MMP in primary feto-placental endothelial cells (fpEC) and trophoblasts isolated from both normal and GDM placentas identified the cells contributing to the GDM-associated changes. A putative MT1-MMP role in angiogenesis was determined using blocking antibodies for in vitro angiogenesis assays. Potential GDM-associated factors and signaling pathways inducing MT1-MMP up-regulation in fpEC were identified using kinase inhibitors. Results: Total and active MT1-MMP was increased in GDM placentas (+51 and 54%, respectively, P < 0.05) as a result of up-regulated expression in fpEC (2.1-fold, P = 0.02). MT1-MMP blocking antibodies reduced in vitro angiogenesis up to 25% (P = 0.03). Pathophysiological levels of insulin and IGF-II, but not IGF-I and glucose, stimulated MT1-MMP expression in fpEC by phosphatidylinositol 3-kinase signals relayed through the insulin, but not IGF-I, receptor. Conclusions: GDM up-regulates MT1-MMP in the feto-placental endothelium, and insulin and IGF-II contribute. This may account for GDM-associated changes in the feto-placental vasculature. (J Clin Endocrinol Metab 97: 3613-3621, 2012)
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Diabetes, Gestational - metabolism
- Endothelial Cells - cytology Endothelial Cells - metabolism
- Female -
- Fetus - metabolism
- Glucose - metabolism
- Humans -
- Hyperglycemia - metabolism
- Insulin - metabolism
- Insulin-Like Growth Factor I - metabolism
- Insulin-Like Growth Factor II - metabolism
- Matrix Metalloproteinase 14 - metabolism
- Neovascularization, Physiologic - physiology
- Placenta - blood supply Placenta - cytology Placenta - metabolism
- Pregnancy -
- Pregnancy Trimester, Third - metabolism
- Primary Cell Culture -
- Trophoblasts - cytology Trophoblasts - metabolism
- Up-Regulation - physiology