Modulation of NRF2/KEAP1 Signaling in Preeclampsia.
Giovanni TossettaSonia FantoneFederica PianiCaterina CrescimannoAndrea CiavattiniStefano Raffaele GiannubiloDaniela MarzioniPublished in: Cells (2023)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- pregnancy outcomes
- reactive oxygen species
- dna damage
- preterm birth
- diabetic rats
- ischemia reperfusion injury
- cell death
- signaling pathway
- cell cycle arrest
- blood pressure
- gestational age
- pregnant women
- systematic review
- early onset
- small molecule
- transcription factor
- hydrogen peroxide
- gene expression
- pi k akt
- endoplasmic reticulum stress
- protein protein
- dna methylation
- genome wide
- epithelial mesenchymal transition
- physical activity
- body mass index