Endonuclease G promotes preeclampsia by regulating the Wnt signaling pathway

Abstract

This study was conducted to investigate the effect and underlying mechanism of endonuclease G (ENDOG) on preeclampsia (PE). Differentially expressed genes in four Gene Expression Omnibus datasets (GSE147776, GSE96984, GSE102897, and GSE65271) were identified using a Venn diagram. Normal and PE placental tissues were collected from normal and PE parturients. The expression of ENDOG in tissues was tested using western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. Cell viability, proliferation, invasion, and migration were detected using Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, transwell, and wound healing assays, respectively. Angiogenesis was detected using tube formation and enzyme-linked immunosorbent assays. Kyoto Encyclopedia of Genes and Genomes analysis was performed to analyze the downstream mechanisms of ENDOG in PE. Wnt pathway-related protein levels were detected using western blotting. ENDOG was highly expressed in preeclampsia tissues and HTR-8/SVneo cells. Overexpression of ENDOG inhibited HTR-8/SVneo cell growth, proliferation, invasion, migration, and angiogenesis. Moreover, the levels of angiopoietin-1 and pathway-related proteins were markedly decreased by ENDOG upregulation. Knockdown of ENDOG had the opposite effects, which were counteracted by the inhibitor of Wnt production-2. ENDOG expression was upregulated in preeclampsia and affected HTR-8/SVneo cell proliferation, invasion, migration, apoptosis, and angiogenesis via the Wnt signaling pathway. This provided a novel strategy for the prevention and treatment of PE.

Graphical Abstract

Keywords:

• Preeclampsia
• endonuclease G
• Wnt signaling pathway
• HTR-8/SVneo cell
• angiogenesis

Acknowledgments

None.

Disclosure statement

Jing Yang declares that he/she has no conflict of interest; Xuejun Kou declares that he/she has no conflict of interest.

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.