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. 2021 Jul;47(7):2406-2416.
doi: 10.1111/jog.14782. Epub 2021 Apr 11.

Integrin β1 regulates proliferation, apoptosis, and migration of trophoblasts through activation of phosphoinositide 3 kinase/protein kinase B signaling

Chang Shu  1 , Shumei Han  2 , Cong Hu  3 , Chen Chen  1 , Bo Qu  1 , Jin He  1 , Shuai Dong  1 , Peng Xu  4
Affiliations

Integrin β1 regulates proliferation, apoptosis, and migration of trophoblasts through activation of phosphoinositide 3 kinase/protein kinase B signaling

Chang Shu et al. J Obstet Gynaecol Res. 2021 Jul.

Abstract

Aims: Abnormal trophoblast invasion is one of the onsets of preeclampsia (PE). Studies found that integrin β1 (ITGB1) is closely related to PE, but the role of ITGB1 in the progression of trophoblast remained unclear. Therefore, we studied the functional role of ITGB1 in PE and its effects on trophoblast.

Methods: ITGB1 expression in placenta tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of transfection on HTR-8/SVneo cells were analyzed by qRT-PCR and western blotting. After cell transfection, colony formation assay, flow cytometry, wound healing assay, and transwell assay were performed to detect cell proliferation, apoptosis, migration, and invasion. Western blotting assay was used for determining phosphoinositide 3 kinase (PI3K) and protein kinase B (Akt) signaling pathway. After inhibiting PI3K/Akt pathway, apoptosis-regulated proteins were detected by western blotting, and the effects of inhibitor on the migration and invasion changes were examined.

Results: ITGB1 was downregulated in placenta tissues from PE patients, as compared with normal. ITGB1 overexpression in HTR-8/SVneo cells enhanced cell proliferation, migration, and invasion, reduced cell apoptosis, and improved phosphorylation of PI3K and Akt. However, ITGB1 depletion resulted in an opposite effect to its overexpression. Inhibition of PI3K/Akt pathway completely blocked the effect of ITGB1 overexpression on cells, because we observed that apoptosis-regulated proteins were highly upregulated, and that cell migration and invasion were reduced.

Conclusion: ITGB1 regulated HTR-8/SVneo cell progression by activation of the PI3K/Akt pathway.

Keywords: integrin β1 (ITGB1); migration; the phosphoinositide 3 kinase (PI3K) and protein kinase B (Akt) pathway; trophoblasts.

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