Polystyrene nanoplastics lead to ferroptosis in the lungs

作者全名："Wu, Yuhao; Wang, Junke; Zhao, Tianxin; Sun, Mang; Xu, Maozhu; Che, Siyi; Pan, Zhengxia; Wu, Chun; Shen, Lianju"

作者地址："[Wu, Yuhao; Pan, Zhengxia; Wu, Chun] Chongqing Med Univ, Dept Cardiothorac Surg, Childrens Hosp, Chongqing, Peoples R China; [Wu, Yuhao; Xu, Maozhu; Che, Siyi; Pan, Zhengxia; Wu, Chun; Shen, Lianju] Chongqing Med Univ, Pediat Res Inst, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,Minist Edu, Chongqing, Peoples R China; [Wang, Junke; Sun, Mang] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhao, Tianxin] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Pediat Surg, Guangzhou, Guangdong, Peoples R China; [Xu, Maozhu; Che, Siyi] Chongqing Med Univ, Dept Resp Med, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Shen, LJ (通讯作者)，Chongqing Med Univ, Pediat Res Inst, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,Minist Edu, Chongqing, Peoples R China."

来源：JOURNAL OF ADVANCED RESEARCH

ESI学科分类：Multidisciplinary

WOS号：WOS:001171012000001

JCR分区：Q1

影响因子：11.4

年份：2024

卷号：56

期号：　

开始页：31

结束页：41

文献类型：Article

关键词：Polystyrene nanoplastics; Ferroptosis; Lung injury; Bronchial epithelial cells

摘要："Introduction: It has been shown that polystyrene nanoplastic (PS-NP) exposure induces toxicity in the lungs. Objectives: This study aims to provide foundational evidence to corroborate that ferroptosis and abnormal HIF-1a activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure. Methods: Fifty male and female C57BL/6 mice were exposed to distilled water or 100 nm or 200 nm PSNPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100 lg/ml, 200 lg/ml and 400 lg/ml 100 or 200 nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24 h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1a/HO-1 signaling pathway activity. Results: H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1a/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury. Conclusion: PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1a/HO-1 signaling pathway, and eventually led to lung injury. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article"

基金机构：Chongqing Medical University Program for Youth Innovation in Future Medicine [W0204]; National Natural Science Foundation of China [81801521]; Clinical Innovation Project of Children's Hospital of Chongqing Medical University [CHCMU-XJS-2022-56]; Guangdong Basic and Applied Basic Research Foundation [2022A1515012576]

基金资助正文："This study was supported by grants from the Chongqing Medical University Program for Youth Innovation in Future Medicine in 2022 (No. W0204), National Natural Science Foundation of China (Grant No. 81801521), Clinical Innovation Project of Children's Hospital of Chongqing Medical University (CHCMU-XJS-2022-56), and the Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515012576)."