Modulation of NRF2/KEAP1 Signaling in Preeclampsia

Cells. 2023 Jun 4;12(11):1545. doi: 10.3390/cells12111545.

Abstract

Placentation is a key and tightly regulated process that ensures the normal development of the placenta and fetal growth. Preeclampsia (PE) is a hypertensive pregnancy-related disorder involving about 5-8% of all pregnancies and clinically characterized by de novo maternal hypertension and proteinuria. In addition, PE pregnancies are also characterized by increased oxidative stress and inflammation. The NRF2/KEAP1 signaling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding to the antioxidant response element (ARE) region present in the promoter of several antioxidant genes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase that neutralize ROS, protecting cells against oxidative stress damages. In this review, we analyze the current literature regarding the role of the NRF2/KEAP1 pathway in preeclamptic pregnancies, discussing the main cellular modulators of this pathway. Moreover, we also discuss the main natural and synthetic compounds that can regulate this pathway in in vivo and in vitro models.

Keywords: KEAP1; NRF2; NRF2/KEAP1; antioxidants; compounds; natural; preeclampsia; pregnancy; pregnancy complications.

Publication types

  • Review

MeSH terms

  • Female
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • Pre-Eclampsia*
  • Pregnancy
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology

Substances

  • Reactive Oxygen Species
  • NF-E2-Related Factor 2
  • Kelch-Like ECH-Associated Protein 1
  • KEAP1 protein, human

Grants and funding

This research received no external funding.