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骨基质细胞抗原 2(BST2)通过下调基质金属蛋白酶 2(MMP2)抑制子痫前期滋养细胞的迁移和侵袭。

Bone marrow stromal cell antigen 2(BST2) suppresses the migration and invasion of trophoblasts in preeclampsia by downregulating matrix metallopeptidase 2(MMP2).

机构信息

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Key Laboratory of Embryo Original Disease, Shanghai, China.

出版信息

Bioengineered. 2022 May;13(5):13174-13187. doi: 10.1080/21655979.2022.2074712.

Abstract

Preeclampsia is a grievous pregnancy-related complication with an incidence of approximately 5∼7% in pregnant women. Placental abnormalities and decreased placental perfusion associated with impaired trophoblast invasion are early pathological findings of preeclampsia. BST2 is a multifunctional transmembrane protein that plays critical roles in physiological and pathological processes, but its impacts and mechanisms of action in preeclampsia are inadequately understood. The aim of this manuscript was to investigate the functional impacts of BST2 and MMP2 on the biological behavior of trophoblast cells in preeclampsia. The expression of these proteins and their genes was analyzed by qRT-PCR, western blotting and immunohistochemistry. The results showed that the expression of BST2 and MMP2 was significantly downregulated in preeclampsia. The migration and invasion capacities of HTR-8/SVneo and JAR cells with overexpression or knockdown of BST2 were detected by wound healing assay and Transwell assays. It was found that BST2 overexpression could up-regulate expression, and enhance the migration and invasion capacity of HTR-8/SVneo and JAR cells. BST2 knockdown could reverse these effects. MMP2 knockdown could downregulate the invasion capacity of HTR-8/SVneo cells, and MMP2 overexpression reversed these effects. Pearson correlation analysis demonstrated that the expression of MMP2 and BST2 were positively correlated. These results indicate that the downregulation of BST2 lowers MMP2 expression and restraint trophoblast functions, which probably explain its role in the pathogenesis of preeclampsia.

摘要

子痫前期是一种严重的妊娠相关并发症,孕妇发病率约为 5∼7%。胎盘异常和胎盘灌注减少与滋养细胞侵袭受损有关,是子痫前期的早期病理发现。BST2 是一种多功能跨膜蛋白,在生理和病理过程中发挥着关键作用,但它在子痫前期中的作用和机制尚不清楚。本手稿旨在研究 BST2 和 MMP2 对子痫前期滋养细胞生物学行为的功能影响。通过 qRT-PCR、western blot 和免疫组化分析这些蛋白及其基因的表达。结果表明,子痫前期 BST2 和 MMP2 的表达明显下调。通过划痕愈合试验和 Transwell 试验检测过表达或敲低 BST2 的 HTR-8/SVneo 和 JAR 细胞的迁移和侵袭能力。结果发现,BST2 过表达可上调 MMP2 表达,并增强 HTR-8/SVneo 和 JAR 细胞的迁移和侵袭能力。BST2 敲低可逆转这些效应。MMP2 敲低可下调 HTR-8/SVneo 细胞的侵袭能力,而过表达 MMP2 可逆转这些效应。Pearson 相关分析表明 MMP2 和 BST2 的表达呈正相关。这些结果表明,BST2 的下调降低了 MMP2 的表达并抑制了滋养细胞的功能,这可能解释了它在子痫前期发病机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3216/9276030/e356e65c30a8/KBIE_A_2074712_UF0001_OC.jpg

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