PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo

Cellular & Molecular Biology Letters

Research

Dong Hun Lee¹  Wei-Hao Wang²  Taeho Kwon³  Ying-Hao Han⁴  Hu-Nan Sun⁴  Chen-Xi Ren⁴  Xiao-Yu Guo⁴  Wan-Qiu Xiao⁴  Jie Cong⁴  Hui-Na Zhang⁴  Nan Li⁴  Ying-Ying Hao⁴  Xiao-Ming Wang⁵ 

[1] Department of Biological Sciences, Research Center of Ecomimetics, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, 61186, Gwangju, Republic of Korea;National Coarse Cereals Engineering Research Center, Heilongjiang Bayi Agricultural University, 163319, Daqing, China;Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 351-33 Neongme-Gil, Ibam-Myeon, Jeongeup-Si, 56216, Jeonbuk, Republic of Korea;Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, 34113, Daejeon, Republic of Korea;Stem Cell and Regenerative Biology Laboratory, College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Xingyang Road #2, 163319, Daqing, Heilongjiang, China;Yabian Academy of Agricultural Science, 1334000, Longjing, Jilin, China;

关键词: Pulmonary fibrosis;    Peroxiredoxin 1;    Reactive oxygen species;    Epithelial-mesenchymal transition;    Cell proliferation;    PI3K/Akt and JNK/Smad signalling pathways;   

DOI  :  10.1186/s11658-023-00460-x

 received in 2023-01-31, accepted in 2023-05-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin.MethodsExperimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study.ResultsPRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-β secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways.ConclusionsOur findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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