DJ-1 Upregulates the Nrf2/GPX4 Signal Pathway to Inhibit Trophoblast Ferroptosis in the Pathogenesis of Preeclampsia

Overview

Journal Sci Rep

Specialty Science

Date 2022 Feb 22

PMID 35190654

Authors

Tingting Liao

Xia Xu

Xu Ye

Jianying Yan

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a newly discovered mode of cell death that involves disorders in iron metabolism and the accumulation of reactive oxygen species (ROS) in the plasma membrane. Preeclampsia (PE) is a gestational idiopathic disease that is characterized by hypertension and albuminuria, begins after 20 weeks of pregnancy. DJ-1 is a prerequisite for activating and stabilizing Nrf2 to allow translocation to the nucleus to carry out further functions. Detecting the expression levels of DJ-1, the Nrf2/GPX4 signaling pathway and ferroptosis markers in placental tissues of pregnant women with and without PE. Analyzing the effects of the ferroptosis inducer (RSL3) and the inhibitor (Fer-1) on the mortality rate of BeWo cells and DJ-1+/+, DJ-1-/- BeWo cells. Ferroptosis markers (MDA concentration and morphology of trophoblast cells) and DJ-1 and its downstream the Nrf2/GPX4 signaling pathway increased significantly in PE pathological state. The expression levels of DJ-1 protein in the control group and the PE group were positively correlated with the expression levels of Nrf2/GPX4 signaling pathway protein, and negatively correlated with the MDA concentration. BeWo cells were sensitive to the ferroptosis inducer (RSL3) and the inhibitor (Fer-1). The high expression levels of DJ-1 in BeWo cells can resist ferroptosis by regulating the Nrf2/GPX4 signaling pathway. Ferroptosis is involved in the pathogenesis of PE. DJ-1 can mediate the trophoblast cells ferroptosis and play a protective role in the pathogenesis of preeclampsia by regulating the Nrf2/GPX4 signaling pathway.

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