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N-乙酰氨基葡萄糖转移酶 III 的表达促进了早期人胎盘滋养层的侵袭和迁移。

Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion and Migration in Early Human Placenta.

机构信息

Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Reprod Sci. 2019 Oct;26(10):1373-1381. doi: 10.1177/1933719118765967. Epub 2018 Apr 11.

Abstract

INTRODUCTION

Trophoblast migration and invasion at the maternal-fetal interface are crucial events for normal placentation and successful pregnancy. This progress is well controlled by many placenta-specific factors. Inadequate trophoblast invasion results in poor placenta plantation or even complications such as preeclampsia. It has been shown that N-acetylglucosaminyltransferase III (GnT-III) participates in tumor invasion and metastasis as a suppressor; however, the expression of GnT-III and its role in normal pregnancy is unclear. Our objective was to characterize GnT-III expression and function during placental development and identify the underlying mechanisms.

METHODS

The expression of GnT-III in human placental tissue from the first trimester was determined by immunohistochemistry. The HTR8/SVneo cell line was used to investigate the effects of GnT-III on proliferation, apoptosis, migration/invasion, matrix metalloproteinase (MMP) 2/9 activity, and the expression of the tissue inhibitor of metalloproteinase (TIMP) 1/2 using cell 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, flow cytometric analysis, transwell migration/invasion assays, gelatin zymography, and Western blot, respectively. Moreover, a placental villous explant model was employed to determine its functions in placentation.

RESULTS

In the first-trimester placental tissue, GnT-III was localized within the cytotrophoblast, the syncytiotrophoblast and the trophoblast columns of human placental villi, decidual cells, and some extravillous cells in the maternal decidua. GnT-III silencing significantly inhibited HTR8/SVneo cell invasion and migration as well as extravillous explant outgrowth. The application of GnT-III siRNA significantly attenuated MMP2/9 activity and increased TIMP1/2 expression.

DISCUSSION AND CONCLUSION

GnT-III is expressed in trophoblasts during normal human pregnancy and is involved in regulating trophoblast function.

摘要

简介

滋养细胞在母体-胎儿界面的迁移和侵袭对于正常胎盘形成和成功妊娠至关重要。这一过程受到许多胎盘特异性因素的严格控制。滋养细胞侵袭不足会导致胎盘种植不良,甚至出现子痫前期等并发症。已有研究表明,N-乙酰氨基葡萄糖基转移酶 III(GnT-III)作为一种抑制因子参与肿瘤的侵袭和转移;然而,GnT-III 的表达及其在正常妊娠中的作用尚不清楚。我们的目的是研究 GnT-III 在胎盘发育过程中的表达和功能,并探讨其潜在的作用机制。

方法

通过免疫组织化学方法检测人早孕胎盘组织中 GnT-III 的表达。采用 HTR8/SVneo 细胞系,通过细胞 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide,MTT)比色法、流式细胞术分析、Transwell 迁移/侵袭实验、明胶酶谱法和 Western blot 检测 GnT-III 对细胞增殖、凋亡、迁移/侵袭、基质金属蛋白酶(matrix metalloproteinase,MMP)2/9 活性以及组织金属蛋白酶抑制剂(tissue inhibitor of metalloproteinase,TIMP)1/2 表达的影响。此外,我们还采用胎盘绒毛外植体模型来确定 GnT-III 在胎盘形成中的功能。

结果

在人早孕胎盘组织中,GnT-III 定位于细胞滋养层、合体滋养层和绒毛滋养细胞柱、蜕膜细胞以及母体蜕膜中的一些绒毛外细胞。GnT-III 沉默显著抑制 HTR8/SVneo 细胞的侵袭和迁移以及绒毛外植体的生长。应用 GnT-III siRNA 可显著降低 MMP2/9 活性并增加 TIMP1/2 的表达。

结论

GnT-III 在正常妊娠的滋养细胞中表达,并参与调节滋养细胞的功能。

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