Peng Chenwen, Wei Jingyan, Chen Wuxia, Liang Fengao, Huang Zhenyan, Huang Ying
Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China.
Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan 528400, China.
iScience. 2025 Aug 18;28(9):113372. doi: 10.1016/j.isci.2025.113372. eCollection 2025 Sep 19.
This study elucidates the pathogenic mechanisms of perfluorooctane sulfonate (PFOS) in chronic obstructive pulmonary disease (COPD) through network toxicology and molecular docking. By integrating multiple databases, we identified 158 PFOS-related targets in COPD, with five key proteins (epidermal growth factor receptor [EGFR], ESR1, GRB2, HSP90AA1, and SRC) showing central roles in protein interaction networks. Functional enrichment analysis revealed their involvement in key pathophysiological processes, including airway inflammatory responses, oxidative stress, and immune regulation, primarily through modulation of cell survival and proliferation pathways and immune and hormonal regulation pathways. Gene set enrichment analysis (GSEA) further validated these findings by confirming the significant enrichment of five key KEGG pathways identified in our analysis. Molecular docking studies confirmed high-affinity binding between PFOS and these core targets, indicating PFOS may dysregulate inflammatory responses, oxidative balance, and cellular proliferation in COPD pathogenesis. These findings provide critical molecular insights into environmental pollutant-aggravated respiratory disorders and highlight potential intervention targets for COPD management.
本研究通过网络毒理学和分子对接阐明了全氟辛烷磺酸（PFOS）在慢性阻塞性肺疾病（COPD）中的致病机制。通过整合多个数据库，我们在COPD中鉴定出158个与PFOS相关的靶点，其中五个关键蛋白（表皮生长因子受体[EGFR]、ESR1、GRB2、HSP90AA1和SRC）在蛋白质相互作用网络中发挥核心作用。功能富集分析表明，它们主要通过调节细胞存活和增殖途径以及免疫和激素调节途径，参与关键的病理生理过程，包括气道炎症反应、氧化应激和免疫调节。基因集富集分析（GSEA）通过确认我们分析中鉴定的五条关键KEGG途径的显著富集，进一步验证了这些发现。分子对接研究证实了PFOS与这些核心靶点之间的高亲和力结合，表明PFOS可能在COPD发病机制中失调炎症反应、氧化平衡和细胞增殖。这些发现为环境污染物加重的呼吸系统疾病提供了关键的分子见解，并突出了COPD管理的潜在干预靶点。
