Sestrin2 Regulates Endoplasmic Reticulum Stress-Dependent Ferroptosis to Engage Pulmonary Fibrosis by Nuclear Factor Erythroid 2-Related Factor 2/Activating Transcription Factor 4 (NRF2/ATF4)

Author:

Dong Zhaoxing1ORCID,Li Ting1,Wang Cenli2,Zhou Yong1,Tong Zhongkai1,Du Xuekui1ORCID

Affiliation:

1. Department of Respiratory and Critical Care Medicine, Ningbo No. 2 Hospital, Ningbo 315000, Zhejiang Province, China

2. Department of Respiratory and Critical Care Medicine, Xiangshan Red Cross Taiwan Compatriot Hospital Medical and Health Group, Ningbo 315000, Zhejiang, China

Abstract

Pulmonary fibrosis (PF) can lead to chronic inflammation, the destruction of alveoli and irreversible lung damage. Sestrin2 is a highly protective stress-inducible protein that is involved in the cell response to various stress factors and the regulation of homeostasis and has a certain protective effect against PF. In this study, TGF-β1 was used to establish a PF cell model. Bleomycin was used to induce PF in mice, and the expression levels of related proteins were detected by western blotting. The levels of the inflammatory cytokine, TNF-α, IL-6, and IL-1β were detected by enzyme-linked immunosorbent assays. Immunoprecipitation was used to verify the interaction between ATF4 and NRF2 and between Sestrin2 and NRF2 to explore the specific mechanism by which Sestrin2 affects PF. The results showed that Sestrin2 inhibited fibroblast-to-myofibroblast transition (FMT), improved inflammation, promoted cell proliferation, and alleviated PF. Activating transcription factor 4/nuclear factor erythroid 2-related factor 2 (NRF2/ATF4) signaling pathway activation could alleviate endoplasmic reticulum stress, inhibit ferroptosis and FMT, and reduce reactive oxygen species levels, thereby alleviating PF. Overexpression of ATF4 and the addition of a ferroptosis inducer reversed Sestrin2-mediated alleviation of PF. In conclusion, Sestrin2 alleviates PF and endoplasmic reticulum stress-dependent ferroptosis through the NRF2/ATF4 pathway.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

Reference47 articles.

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3