Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis

doi:10.1016/j.envint.2022.107706

	Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis
	Yue, Dayong 1; Zhang, Qian 3; Zhang, Jinjin 1; Liu, Weili 2; Chen, Libang 1; Wang, Meirong 2; Li, Rongrong 2; Qin, Song4 ; Song, Xiaodong 1; Ji, Yunxia 1,2
发表期刊	ENVIRONMENT INTERNATIONAL
ISSN	0160-4120
	2023
卷号	171 页码:17
关键词	PM2 5 Pulmonary fibrosis HO-1 Ferritinophagy Ferroptosis
DOI	10.1016/j.envint.2022.107706
通讯作者	Qin, Song(sqin@yic.ac.cn) ; Song, Xiaodong(songxd71@163.com) ; Ji, Yunxia(yxji@yic.ac.cn)
英文摘要	Fine particulate matter (PM2.5) has been widely reported to contribute to the pathogenesis of pulmonary dis-eases. The direct hazardous effect of PM2.5 on the respiratory system at high concentrations in vitro and in vivo have been well identified. However, its effect on the pre-existing respiratory diseases of patients at environment-related concentrations remains unclear. Diesel exhaust PM2.5 as a primary representative of ambient PM2.5 fine particles were used to investigated the effect of PM2.5 on the fibrosis progression of existing pulmonary fibrosis disease models. This study reported that PM2.5 could result in the enhanced sensitivity to fibrotic response, which may be ascribed to ferroptosis induced by PM2.5 in damaged lung areas. Proteomic analysis revealed that the upregulation of HO-1 as a key mechanism in the ferroptosis and exacerbation of pulmonary fibrosis induced by PM2.5. As a result, HO-1 degraded heme-containing protein and released iron in fibrotic cells, leading to generation of mitochondrial ROS and impaired mitochondrial function. Transmission electron microscopic assay verified that PM2.5 entered the mitochondria of fibrotic cells and was accompanied by significant mitochondrial morphological changes characterized by increased mitochondrial membrane density and reduced mitochondrial size. The HO-1 inhibitor zinc protoporphyrin and mitochondrion-targeted antioxidant Mito-TEMPO significantly attenuated PM2.5-induced ferroptosis and exacerbation of fibrosis. In addition, AMPK-ULK1 axis-triggered autophagy activation and NCOA4-mediated degradation of ferritin by autophagy were found to be related to the PM2.5-induced ferroptosis of fibrotic cells. As evidenced by the inhibition of autophagy with 3-methyladenine or AMPK inhibitor, NCOA4 knockdown decreased intracellular iron accumulation and lipid peroxidation, thereby relieving PM2.5-induced epithelial-mesenchymal transition and cell death in fibrotic cells. Overall, this study provided experimental support for the idea that PM2.5 greatly deteriorates fibrosis process in pre-existing pul-monary fibrosis, and HO-1-mediated mitochondrial dysfunction and NCOA4-mediated ferritinophagy are jointly required for the PM2.5-induced ferroptosis and enhanced fibrosis effects.
资助机构	National Nature Science Foundation of China ; Natural Science Foundation of Shandong Province ; Start-up Fund for doctoral research program ; Clinical+X Scientific Innovation Project of Binzhou Medical University ; regenerative medicine research program of Xu Rongxiang
收录类别	SCI
语种	英语
关键词[WOS]	FINE PARTICULATE MATTER ; AUTOPHAGY ; CELLS ; INFLAMMATION ; DEGRADATION ; INHIBITION ; EXPRESSION ; EXPOSURE ; HEALTH ; SIGNAL
研究领域[WOS]	Environmental Sciences & Ecology
WOS记录号	WOS:000910641400001
引用统计	被引频次：18[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.yic.ac.cn/handle/133337/32550
专题	海岸带生物学与生物资源利用重点实验室海岸带生物学与生物资源利用重点实验室_海岸带生物学与生物资源保护实验室
通讯作者	Qin, Song; Song, Xiaodong; Ji, Yunxia
作者单位	1.Binzhou Med Univ, Sch Pharmaceut Sci, Dept Cellular & Genet Med, Yantai 264003, Peoples R China 2.Binzhou Med Univ, Binzhou Med Univ Hosp, Dept Resp & Crit Care Med, Binzhou 256603, Peoples R China 3.Binzhou Med Univ, Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256603, Peoples R China 4.Chinese Acad Sci, Yantai Inst Costal Zone Res, Key Lab Biol & Bioresource Utilizat, Yantai 264003, Peoples R China
推荐引用方式 GB/T 7714	Yue, Dayong,Zhang, Qian,Zhang, Jinjin,et al. Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis[J]. ENVIRONMENT INTERNATIONAL,2023,171:17.
APA	Yue, Dayong.,Zhang, Qian.,Zhang, Jinjin.,Liu, Weili.,Chen, Libang.,...&Ji, Yunxia.(2023).Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis.ENVIRONMENT INTERNATIONAL,171,17.
MLA	Yue, Dayong,et al."Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis".ENVIRONMENT INTERNATIONAL 171(2023):17.