MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-α Levels
MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-α Levels Ursula Hiden 1 , Elisabeth Glitzner 1 , Marina Ivanisevic 2 , Josip Djelmis 2 , Christian Wadsack 1 , Uwe Lang 1 and Gernot Desoye 1 1 Departmen...
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| Vydané v: | Diabetes (New York, N.Y.) Ročník 57; číslo 1; s. 150 - 157 |
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| Hlavní autori: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
American Diabetes Association
01.01.2008
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| Predmet: | |
| ISSN: | 0012-1797, 1939-327X, 1939-327X |
| On-line prístup: | Získať plný text |
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| Shrnutí: | MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and
Tumor Necrosis Factor-α Levels
Ursula Hiden 1 ,
Elisabeth Glitzner 1 ,
Marina Ivanisevic 2 ,
Josip Djelmis 2 ,
Christian Wadsack 1 ,
Uwe Lang 1 and
Gernot Desoye 1
1 Department of Obstetrics and Gynecology, Medical University of Graz, Austria
2 Department of Obstetrics and Gynecology, University Hospital, Petrova, Zagreb, Croatia
Address correspondence and reprint requests to Ursula Hiden, MSc, PhD, Department of Obstetrics and Gynecology, Medical University
of Graz, Auenbruggerplatz 14, 8036 Graz, Austria. E-mail: ursula.hiden{at}klinikum-graz.at
Abstract
OBJECTIVE —In pregestational diabetes, the placenta at term of gestation is characterized by various structural and functional changes.
Whether similar alterations occur in the first trimester has remained elusive. Placental development requires proper trophoblast
invasion and tissue remodeling, processes involving matrix metalloproteinases (MMPs) of which the membrane-anchored members
(MT-MMPs) such as MT1-MMPs are key players. Here, we hypothesize a dysregulation of placental MT1-MMP in the first trimester
of type 1 diabetic pregnancies induced by the diabetic environment.
RESEARCH DESIGN AND METHODS —MT1-MMP protein was measured in first-trimester placentas of healthy ( n = 13) and type 1 diabetic ( n = 13) women. To identify potential regulators, first-trimester trophoblasts were cultured under hyperglycemia and various
insulin, IGF-I, IGF-II, and tumor necrosis factor-α (TNF-α) concentrations in presence or absence of signaling pathway inhibitors.
RESULTS —MT1-MMP was strongly expressed in first-trimester trophoblasts. In type 1 diabetes, placental pro–MT1-MMP was upregulated,
whereas active MT1-MMP expression was only increased in late first trimester. In isolated primary trophoblasts, insulin, IGF-I,
IGF-II, and TNF-α upregulated MT1-MMP expression, whereas glucose had no effect. The insulin effect was dependent on phosphatidylinositol
3-kinase, the IGF-I effect on mitogen-activated protein kinase, and the IGF-II effect on both.
CONCLUSIONS —This is the first study reporting alterations in the first-trimester placenta in type 1 diabetes. The upregulated MT1-MMP
expression in type 1 diabetes may be the result of higher maternal insulin and TNF-α levels. We speculate that the elevated
MT1-MMP will affect placental development and may thus contribute to long-term structural alterations in the placenta in pregestational
diabetes.
DMEM, Dulbecco's modified Eagle's medium
ECM, extracellular matrix
ERK, extracellular signal–related kinase
GRO, growth-regulated protein
hCG, human chorionic gonadotropin
HIF-1, hypoxia-inducible factor 1
IL, interleukin
MAPK, mitogen-activated protein kinase
MEK1, MAPK/ERK kinase 1
MMP, matrix metalloproteinase
PI 3-kinase, phosphatidylinositol 3-kinase
RPL30, ribosomal protein L30
TNF-α, tumor necrosis factor-α
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 17 October 2007. DOI: 10.2337/db07-0903.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted October 3, 2007.
Received July 4, 2007.
DIABETES |
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| Bibliografia: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0012-1797 1939-327X 1939-327X |
| DOI: | 10.2337/db07-0903 |