USP22 promotes aspirin-induced trophoblast cell proliferation as well as migration via Wnt/β-catenin pathway in preeclampsia

Abstract

Purpose: To investigate the involvement of ubiquitin-specific peptidase 22 (USP22) in the pathogenesis of preeclampsia (PE), and the potential  mechanism of action. Methods: To investigate the role of USP22 in preeclampsia, immunoblot assay as well as quantitative real-time polymerase chain  reaction (qRT-PCR) were conducted to determine USP22 expression levels in placental tissues from both the control (non-preeclampsia normal) and the  PE cases. Furthermore, cell counting kit-8 as well as EdU assays were performed to assess the impact of USP22 on the viability of HTR-8/Svneo and TEV-1  cells. Furthermore, wound closure and Transwell assays were used to examine the effect of USP22 on cell motility, while tube formation assay was used  to determine the effect of USP22 on the angiogenesis of trophoblast cells. Finally, the effect of USP22 on Wnt/β-catenin pathway in HTR-8/Svneo and  TEV-1 human trophoblast cells was evaluated by immunoblot analysis. Results: USP22 expression was significantly reduced in PE placental tissue  compared to control tissues. In addition, USP22 promoted trophoblast cell proliferation, increased cell motility as well as enhanced angiogenesis capacity.  USP22 regulated the proliferation as well as migration of trophoblast cells via Wnt/β-catenin pathway. Notably, USP22 enhanced cell  proliferation and migration in aspirininduced PE. Conclusion: USP22 plays a crucial role in inhibiting trophoblast cell growth by regulating Wnt/β-catenin   pathway. Therefore, targeting USP22 may hold promise for the treatment of PE.