Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells
Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells
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DOI：
10.1095/biolreprod.107.063743
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Schatz, Frederick
中科院分区：
文献类型：
--
作者：
Lockwood, Charles J.;Oner, Ceyda;Schatz, Frederick
绒毛外滋养层细胞（EVT）通过整合素介导的细胞外基质（ECM）中基底膜蛋白的顺序结合和蛋白水解侵入人蜕膜。在先兆子痫中，浅EVT侵犯损害螺旋动脉和小动脉重塑，从而减少子宫胎盘血流量。过量的蜕膜细胞表达的基质金属蛋白酶（MMPs）2和9，对先兆子痫相关的白细胞介素1 β（IL 1B）和肿瘤坏死因子α（TNF）的反应，可能不适当地降解这些基底膜蛋白，并阻碍EVT的侵袭。这项研究发现，与胎龄匹配的对照女性相比，先兆子痫胎盘切片中的蜕膜细胞和邻近间质滋养层细胞中的免疫组织化学MMP 9水平显着更高。相比之下，MMP 2和基质金属蛋白酶组织抑制剂1和2（TIMP 1和TIMP 2）的免疫染色在先兆子痫组和对照组相似。孕早期蜕膜细胞与雌二醇（E-2）或E-2 +醋酸甲羟孕酮（MPA）孵育，有或没有TNF或IL-1B。如通过ELISA测量的，两种细胞因子引起分泌的MMP 9水平的浓度依赖性增加，其不受MPA的影响。相比之下，MMP 2、TIMP 1和TIMP 2的分泌水平在所有给药组中均无变化。底物凝胶酶谱和Western印迹证实，每种细胞因子增加MMP 9的分泌水平，但不增加MMP 2。类似地，定量RT-PCR发现TNF和IL 1B增强MMP 9，但不增强MMP 2的mRNA水平。在着床部位，炎性酪氨酸增强的MMP 9可能通过破坏蜕膜ECM干扰正常的逐步EVT侵袭而促进先兆子痫。
Extravillous trophoblasts (EVTs) invade human decidua via sequential integrin-mediated binding and proteolysis of basement membrane proteins in the extracellular matrix (ECM). In preeclampsia, shallow EVT invasion impairs spiral artery and arteriole remodeling to reduce uteroplacental blood flow. Excess decidual cell-expressed matrix metalloproteinases (MMPs) 2 and 9, in response to preeclampsia-related interleukin 1 beta (IL1B) and tumor necrosis factor alpha (TNF), may inappropriately degrade these basement membrane proteins and impede EVT invasion. This study found significantly higher immunohistochemical MMP9 levels in decidual cells and adjacent interstitial trophoblasts in placental sections of preeclamptic versus gestational age-matched control women. In contrast, immunostaining for MMP2 and tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP1 and TIMP2) were similar in preeclamptic and control groups. First-trimester decidual cells were incubated with estradiol (E-2) or E-2 + medroxyprogesterone acetate (MPA), with or without TNF or IL1B. As measured by ELISA, both cytokines elicited concentration-dependent increases in secreted MMP9 levels that were unaffected by MPA. In contrast, secreted levels of MMP2, TIMP1, and TIMP2 were unchanged in all treatment groups. Substrate gel zymography and Western blotting confirmed that each cytokine increased secreted levels of MMP9 but not MMP2. Similarly, quantitative RT-PCR found that TNF and IL1B enhanced MMP9, but not MMP2, mRNA levels. At the implantation site, inflammatory cytokine-enhanced MMP9 may promote preeclampsia by disrupting the decidual ECM to interfere with normal stepwise EVT invasion.