Transcription factor NF-E2-related factor 2 plays a critical role in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) by regulating ferroptosis

Abstract

NRF2 is an important transcription factor that regulates redox homeostasis in vivo and exerts its anti-oxidative stress and anti-inflammatory response by binding to the ARE to activate and regulate the transcription of downstream protective protein genes, reducing the release of reactive oxygen species. Ferroptosis is a novel iron-dependent, lipid peroxidation-driven cell death mode, and recent studies have shown that ferroptosis is closely associated with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). NRF2 is able to regulate ferroptosis through the regulation of the transcription of its target genes to ameliorate ALI/ARDS. Therefore, This article focuses on how NRF2 plays a role in ALI/ARDS by regulating ferroptosis. We further reviewed the literature and deeply analyzed the signaling pathways related to ferroptosis which were regulated by NRF2. Additionally, we sorted out the chemical molecules targeting NRF2 that are effective for ALI/ARDS. This review provides a relevant theoretical basis for further research on this theory and the prevention and treatment of ALI/ARDS. The intended audience is clinicians and researchers in the field of respiratory disease.