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整合素β3(ITGB3)在子痫前期妊娠中表达降低及其对滋养层细胞生物学行为的影响。

ITGB3 is reduced in pregnancies with preeclampsia and its influence on biological behavior of trophoblast cells.

作者信息

Li Chunyan, Meng Yanan, Zhou Beibei, Zhang Yanrong, Xia Qing, Huang Yu, Meng Li, Shan Chunjian, Xia Jiaai, Zhang Xiangdi, Wang Qiuhong, Lv Mingming, Long Wei

机构信息

Department of Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, No.123, Tianfeixiang, Mochou Rd, Nanjing, 210004, China.

Center for High Performance Computing and System Simulation, Pilot National Laboratory for Marine Science and Technology, Qingdao, 266237, China.

出版信息

Mol Med. 2024 Dec 25;30(1):275. doi: 10.1186/s10020-024-01050-z.

Abstract

BACKGROUND

Preeclampsia (PE) is a serious pregnancy complication associated with impaired trophoblast function. Integrin β3 (ITGB3) is a cell adhesion molecule that plays a role in cell movement. The objective of this study was to identify the biological function and expression level of ITGB3 in PE.

METHODS

Cell proliferation, migration, invasion, adhesion, and apoptosis were estimated by CCK8 assay, transwell, scratch assays, and flow cytometry, respectively. The expression levels of ITGB3 were determined by qRT-PCR, western blot, and immunohistochemistry (IHC). Co-immunoprecipitation and Alphafold-Multimer protein complex structure prediction software were employed to identify the molecules that interact with ITGB3.

RESULTS

Cell functional experiments conducted on HTR8/SVneo cells demonstrated that ITGB3 significantly enhanced proliferation, migration, invasion, and adhesion, while simultaneously inhibiting apoptosis. Relative ITGB3 expression levels were observed to be lower in PE placental tissue than in normal tissue and similarly reduced in hypoxic HTR8/SVneo cells. RNA-sequencing data from PE placental samples in the GEO database were analyzed to identify differentially expressed genes associated with the disease. We identified a total of 1460 mRNAs that were significantly differentially expressed in PE patients. Specifically, 798 mRNAs were significantly upregulated, and 662 mRNAs were significantly downregulated. Notably, the ITGB3 exhibited a pronounced down-regulation among the differential expression mRNA.

CONCLUSIONS

This study suggested that ITGB3 plays an important role in promoting the proliferative, migratory, invasive, and adhesive capabilities of trophoblast cells. These findings may facilitate a more in-depth understanding of the molecular mechanisms that promote PE progression.

摘要

背景

子痫前期(PE)是一种与滋养细胞功能受损相关的严重妊娠并发症。整合素β3(ITGB3)是一种在细胞运动中起作用的细胞粘附分子。本研究的目的是确定ITGB3在PE中的生物学功能和表达水平。

方法

分别通过CCK8检测、Transwell实验、划痕实验和流式细胞术评估细胞增殖、迁移、侵袭、粘附和凋亡情况。采用qRT-PCR、蛋白质免疫印迹法和免疫组织化学(IHC)检测ITGB3的表达水平。利用免疫共沉淀和Alphafold-Multimer蛋白质复合物结构预测软件鉴定与ITGB3相互作用的分子。

结果

对HTR8/SVneo细胞进行的细胞功能实验表明,ITGB3显著增强细胞增殖、迁移、侵袭和粘附能力,同时抑制细胞凋亡。观察到PE胎盘组织中ITGB3的相对表达水平低于正常组织,在缺氧的HTR8/SVneo细胞中也有类似程度的降低。分析了GEO数据库中PE胎盘样本的RNA测序数据,以鉴定与该疾病相关的差异表达基因。我们共鉴定出1460个在PE患者中显著差异表达的mRNA。具体而言,798个mRNA显著上调,662个mRNA显著下调。值得注意的是,ITGB3在差异表达的mRNA中表现出明显下调。

结论

本研究表明,ITGB3在促进滋养层细胞的增殖、迁移、侵袭和粘附能力方面发挥重要作用。这些发现可能有助于更深入地了解促进PE进展的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d760/11670450/52febdb6fc6c/10020_2024_1050_Fig1_HTML.jpg

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