Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Abnormal trophoblast cell apoptosis is implicated in the pathogenesis of pregnancy-related disorders including preeclampsia (PE), and endoplasmic reticulum (ER) stress has been considered as a novel pathway in the regulation of cell apoptosis. In this study, we observed that both apoptosis and ER stress are triggered in trophoblast cells under hypoxia as well as in the placenta of PE rats. Quantitative polymerase chain reaction and Western blot analysis showed that the expression of endoplasmic reticulum disulfide oxidase 1α (ERO1α) is suppressed in trophoblast cells under hypoxia due to the hypermethylation of the ERO1α promoter region, and the inhibition of ERO1α expression plays an important role in ER stress and trophoblast cell apoptosis. Furthermore, we found that DNA methyltransferase 1 (DNMT1) is a key methyltransferase for DNA methylation in the regulation of ERO1α expression, and the binding level of DNMT1 to the ERO1α promoter is markedly elevated under hypoxia although DNMT1 expression is inhibited by hypoxia, suggesting that the binding level of DNMT1 to the ERO1α promoter region rather than the DNMT1 expression level contributes to the hypermethylation of ERO1α. Taken together, these results demonstrate that the hypermethylation of ERO1α mediated by increased binding of DNMT1 to the ERO1α promoter leads to trophoblast cell apoptosis through ER stress in the placenta of PE rats, which shed insight into the etiology of PE and might present a validated therapeutic target for the treatment of PE.

Detaljer

Författare
  • Jiantuan Xiong
  • Ning Ding
  • Tingting Gao
  • Yanhua Wang
  • Wei Guo
  • Hui Zhang
  • Xiaoli Ma
  • Fan Li
  • Jianmin Sun
  • Xiaoling Yang
  • Kai Wu
  • Huiping Zhang
  • Yideng Jiang
Enheter & grupper
Externa organisationer
  • Ningxia Medical University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Sidor (från-till)8588-8599
TidskriftJournal of Cellular Biochemistry
Volym119
Utgåva nummer10
Tidigt onlinedatum2018 jul 30
StatusPublished - 2018
PublikationskategoriForskning
Peer review utfördJa