Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing Normal University, Beijing, 100875, China.
Respir Res. 2022 Jun 15;23(1):156. doi: 10.1186/s12931-022-02070-1.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles.
This study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC-MS/MS analysis.
A total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway, and response to lead ion were significantly enriched at week 2 and 4. Another four processes were only enriched at week 8, namely response to oxidative stress, positive regulation of cell proliferation, thyroid hormone generation, and positive regulation of apoptotic process. The PPI network indicated that these differential proteins were biologically connected in CS-exposed rats. Of the 79 differential proteins in CS-exposed rats, 56 had human orthologs. Seven proteins that had changed at week 2 and 4 when there were no changes of pulmonary function and pathological morphology were verified as potential biomarkers for early screening of CS-induced COPD by proteomic analysis. Another six proteins that changed at week 8 when obvious airflow obstruction was detected were verified as potential biomarkers for prognostic assessment of CS-induced COPD.
These results reveal that the urinary proteome could sensitively reflect pathological changes in CS-exposed rats, and provide valuable clues for exploring COPD biomarkers.
慢性阻塞性肺疾病（COPD）是一种由吸入香烟烟雾（CS）和其他有害气体和颗粒引起的慢性炎症性气道疾病。
本研究旨在基于 LC-MS/MS 分析探索 CS 诱导 COPD 的潜在尿液生物标志物。
共鉴定出 340 种尿液蛋白，其中 79 种差异显著（第 2、4 和 8 周分别为 30、31 和 37 种）。差异尿液蛋白的 GO 注释显示，急性期反应、对有机环状化合物的反应、补体激活经典途径和对铅离子的反应在第 2 和 4 周显著富集。另外四个过程仅在第 8 周富集，即对氧化应激的反应、细胞增殖的正调节、甲状腺激素生成和细胞凋亡过程的正调节。PPI 网络表明，这些差异蛋白在 CS 暴露大鼠中具有生物学联系。在 CS 暴露大鼠的 79 种差异蛋白中，有 56 种具有人类同源物。通过蛋白质组学分析，验证了在第 2 和 4 周时没有改变肺功能和病理形态的 7 种差异蛋白作为 CS 诱导 COPD 早期筛选的潜在生物标志物。在检测到明显气流阻塞的第 8 周时，另外 6 种差异蛋白被验证为 CS 诱导 COPD 预后评估的潜在生物标志物。
这些结果表明尿液蛋白质组可以敏感地反映 CS 暴露大鼠的病理变化，为探索 COPD 生物标志物提供了有价值的线索。
