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

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.