Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture
Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture
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DOI：
10.1071/rd01036
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发表时间：
2001-01-01
影响因子：
1.9
通讯作者：
González, E
中科院分区：
文献类型：
--
作者：
Novaro, V;Colman-Lerner, A;González, E
胚胎着床过程需要广泛的子宫内膜细胞外基质重塑，这一功能主要由基质降解金属蛋白酶(MMPs)执行。在本研究中，我们使用从人足月胎盘分离的滋养层细胞来研究一氧化氮(NO)对单核细胞的调节。结合酶谱、Western印迹和间接免疫荧光，我们发现在低运动性细胞滋养层细胞向高运动性和分化的合体滋养层多核细胞转化过程中，基质金属蛋白酶-2和基质金属蛋白酶-9的表达增加。我们还观察到在这一细胞分化过程中，一氧化氮的产生和一氧化氮合酶(NOS)的表达增加。NO供体(NOC-18和精胺-NOate)或一氧化氮合酶底物(L-精氨酸)刺激滋养层细胞，而一氧化氮合酶抑制剂(N-G-硝基-L-精氨酸甲酯和N-G-单甲基-L-精氨酸)抑制滋养层细胞基质金属蛋白酶-2和基质金属蛋白酶-9的表达和明胶溶解活性。综上所述，这些结果表明，在滋养层细胞分化过程中，NO调节着胚胎着床过程中侵袭所需的基质降解酶的诱导。
The process of embryo implantation requires extensive remodelling of the endometrial extracellular matrix, a function largely performed by matrix-degrading metalloproteinases (MMPs). In the present study, we used trophoblast cells isolated from human term placentas to study the regulation of MNMs by nitric oxide (NO). Using a combination of zymography, Western blot and indirect immunofluorescence, we showed that MMP-2 and MMP-9 are increased during the conversion from low-motile cytotrophoblast cells to the highly motile and differentiated syncytiotrophoblast multinucleated cells. We also observed an increase in NO production and NO synthase (NOS) expression during this cellular differentiation process. In addition, we demonstrated a positive regulatory role of NO on the activity and protein expression of MMP-2 and MMP-9, because NO donors (NOC-18 and spermine-NONOate) or the NOS substrate (L-arginine) stimulate, whereas NOS inhibitors (N-G-nitro-L-arginine methyl ester and N-G-monomethyl-L-arginine) reduce the expression and gelatinolytic activity of MMP-2 and MMP-9 in isolated trophoblast cells. Taken together, these results suggest that, in differentiating trophoblasts, NO regulates the induction of matrix-degrading proteases required for invasion during embryo implantation.