Endonuclease G promotes preeclampsia by regulating the Wnt signaling pathway

Autoimmunity. 2023 Dec;56(1):2182741. doi: 10.1080/08916934.2023.2182741.

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.

Keywords: HTR-8/SVneo cell; Preeclampsia; Wnt signaling pathway; angiogenesis; endonuclease G.

MeSH terms

  • Apoptosis / genetics
  • Female
  • Humans
  • Placenta*
  • Pre-Eclampsia* / genetics
  • Pregnancy
  • Wnt Signaling Pathway

Substances

  • endonuclease G