Loss of interferon regulatory factor-1 prevents lung fibrosis by upregulation of pon1 expression

作者：Aiyuan Zhou, Xiyan Zhang, Xinyue Hu, Tiao Li, Wenzhong Peng, Hang Yang, Dingding Deng, Chunheng Mo, Rongli Lu, Pinhua Pan · 发表于：Respiratory Research · 年份：2024 · DOI：10.1186/s12931-024-02987-9 · 被引用次数：10 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Pulmonary Hypertension Research and Treatments、Paraoxonase enzyme and polymorphisms

Interferon regulatory factor-1 (IRF1) is a transcription factor that plays a significant role in various biological processes, including inflammatory injury, viral infection, cell death, and immune responses, and it has been extensively studied in the context of different lung diseases. However, the mechanism underlying its involvement in lung fibrosis remains largely unknown. Wild type (WT) mice, IRF1 global-null mice ( Irf1 −/− ) were subjected to a bleomycin-induced lung fibrosis model to enable examination of the role of IRF1 in lung fibrosis. Proteomic analysis of lung tissue from WT and Irf1 −/− mice treated with saline or bleomycin was performed to explore the mechanism of IRF1 in regulating lung fibrosis. In the bleomycin-induced fibrosis mouse model, increased expression of IRF1 was observed. Irf1 knockout mice displayed decreased lung fibrosis relative to WT mice following treatment with bleomycin. The protein expression of fibronectin, as assessed by the Western blot analysis of lung tissues, was downregulated in Irf1 −/− mice. We observed a similar reduction in collagen content using hydroxyproline detection. Histologically, there was less collagen deposition in the lungs of Irf1 −/− mice compared with WT mice. Proteomics data revealed that IRF1 may be involved in lung fibrosis via the regulation of ferroptosis. We determined that paraoxonase 1(PON1), a poorly characterized protein in lung fibrosis, was upregulated in Irf1 −/− mice following exposure to bleomycin....