Research Paper Volume 12, Issue 13 pp 12943—12959
Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1
- 1 Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Centre for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai 200011, China
Received: January 9, 2020 Accepted: May 22, 2020 Published: June 29, 2020https://doi.org/10.18632/aging.103378
How to Cite
Copyright © 2020 Dong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute lung injury (ALI) is a syndrome associated with a high mortality rate. Nrf2 is a key regulator of intracellular oxidation homeostasis that plays a pivotal role in controlling lipid peroxidation, which is closely related to the process of ferroptosis. However, the intrinsic effect of Nrf2 on ferroptosis remains to be investigated in ALI. We found that MDA expression increased while GSH and GPX4 decreased in ALI models. Furthermore, the characteristic mitochondrial morphological changes of ferroptosis appear in type II alveolar epithelial cells in IIR models. Additional pre-treatment of Fe and Ferrostatin-1 in ALI significantly aggravated or ameliorated the pathological injuries of lung tissue, pulmonary edema, lipid peroxidation, as well as promoted or prevented cell death, respectively. Knocking down Nrf2 notably decreased the expression of SLC7A11 and HO-1. Interference with SLC7A11 markedly increased Nrf2-HO-1 and dramatically attenuated cell death in OGD/R models. These findings indicate that ferroptosis can be inhibited by Nrf2 through regulating SLC7A11 and HO-1, which may provide a potential therapeutic strategy for IIR-ALI.