KEAP1型
百草枯
肺纤维化
脂质过氧化
氧化应激
信号转导
纤维化
细胞凋亡
标记法
生物
化学
癌症研究
细胞生物学
生物化学
医学
病理
转录因子
基因
作者
Xiaoxia Yang,Ping Xiao,Xiaofeng Shi
标识
DOI:10.1007/s11033-023-08756-z
摘要
Abstract Paraquat (PQ) is a widely used and highly toxic pesticide that is often actively ingested and causes pulmonary fibrosis in patients. Ferroptosis is a regulated form of non-apoptotic cell death associated with iron-dependent lipid peroxidation. Previous studies have shown that ferroptosis is involved in the occurrence and development of acute lung injury (ALI). In this study, a model rat with inflammatory response, oxidative stress, lipid peroxidation, and pulmonary fibrosis was successfully established by PQ administration. The occurrence of ferroptosis in PQ model rats was confirmed by TUNEL staining, iron ion detection, and Ferroptosis related biomarkers detection. Western blotting (WB) and real-time PCR (RT-PCR) showed that the expression of Keap1 was significantly up-regulated and the expression of Nrf2 was significantly down-regulated in the lung tissue of PQ rats. Further transcriptomics and proteomics confirmed: (1) Enrichment of molecular processes related to iron ion binding; (2) Keap1 may promote Nrf2 ubiquitination and lead to Nrf2 degradation; (3) There is functional enrichment in ferroptosis related pathways. Our results suggest that PQ can regulate Keap1/Nrf2 signaling pathway, leading to increased lipid peroxidation and abnormal iron uptake, thereby inducing iron death and exacerbating the progression of pulmonary fibrosis. Our study provides new insights into PQ-induced pulmonary fibrosis. Graphical abstract
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