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
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DOI：
10.2337/db07-0903
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发表时间：
2008-01-01
期刊：
影响因子：
7.7
通讯作者：
Desoye, Gernot
中科院分区：
文献类型：
--
作者：
Hiden, Ursula;Glitzner, Elisabeth;Desoye, Gernot
目的-在妊娠前糖尿病中，足月胎盘的特征是各种结构和功能变化。类似的改变是否发生在妊娠前三个月仍然难以捉摸。胎盘发育需要适当的滋养层侵袭和组织重塑，这些过程涉及基质金属蛋白酶 (MMP)，其中膜锚定成员 (MT-MMP) 如 MT1-MMP 是关键参与者。在此，我们假设由糖尿病环境引起的 1 型糖尿病妊娠早期胎盘 MT1-MMP 失调。 研究设计和方法 - 在健康 (n = 13) 和 1 型糖尿病 (n = 13) 女性的妊娠早期胎盘中测量 MT1-MMP 蛋白。为了鉴定潜在的调节因子，在存在或不存在信号通路抑制剂的情况下，在高血糖和各种胰岛素、IGF-I、IGF-II 和肿瘤坏死因子-α (TNF-α) 浓度下培养妊娠早期滋养细胞。 结果-MT1-MMP 在妊娠早期滋养细胞中强烈表达。在 1 型糖尿病中，胎盘 MT1-MMP 前体表达上调，而活性 MT1-MMP 表达仅在妊娠早期后期增加。在分离的初级滋养层细胞中，胰岛素、IGF-I、IGF-II 和 TNF-a 上调 MT1-MMP 表达，而葡萄糖则没有影响。胰岛素作用取决于磷脂酰肌醇 3-激酶、IGF-I 对丝裂原激活蛋白激酶的作用以及 IGF-II 对两者的作用。 结论——这是第一项报告 I 型糖尿病妊娠早期胎盘变化的研究。 I 型糖尿病中 MT1-MMP 表达上调可能是母体胰岛素和 TNF-a 水平较高的结果。水平。我们推测升高的 MT1-MMP 将影响胎盘发育，因此可能导致妊娠前糖尿病胎盘的长期结构改变。
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-alpha (TNF-alpha) 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-a 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 I diabetes. The upregulated MT1-MMP expression in type I diabetes may be the result of higher maternal insulin and TNF-a. 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.