Proteome Profiling of Lung Tissues in Chronic Obstructive Pulmonary Disease (COPD): Platelet and Macrophage Dysfunction Contribute to the Pathogenesis of COPD
Proteome Profiling of Lung Tissues in Chronic Obstructive Pulmonary Disease (COPD): Platelet and Macrophage Dysfunction Contribute to the Pathogenesis of COPD
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DOI：
10.2147/copd.s246845
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发表时间：
2020-01-01
影响因子：
2.8
通讯作者：
Ge, Wei
中科院分区：
文献类型：
--
作者：
Liu, Yifan;Liu, Haotian;Ge, Wei
目的：慢性阻塞性肺疾病（COPD）是一个全球性的公共卫生挑战，由于其高患病率和相关的残疾和死亡率;然而，COPD的发病机制仍不清楚。在这项研究中，我们的目的是确定关键蛋白质参与的发病机制，COPD.Patients和方法：我们收集肺组织从三名COPD患者需要胸外科肺移植在中日友谊医院。通过北京协和医学院（中国）的全身捐赠计划，收集来自三名无肺部疾病史的供体的肺组织作为健康对照。我们使用高分辨率液相色谱与串联质谱相结合的方法对两组中的蛋白质表达谱进行了蛋白质组学分析（LC-MS/MS）和定量6重串联质量标签标记;这些数据通过蛋白质印迹分析验证。共鉴定和分析了4976种蛋白质，其中173种发生了显著变化（118种下调，55种上调）。基因本体分析和蛋白质相互作用网络表明，显著改变的蛋白质，特别是下调的蛋白质，参与血小板和巨噬细胞活化。质谱蛋白质组学数据已通过iProX合作伙伴库存入ProteomeXchange Consortium（htty：proteomecentral.proteomexchange.org），数据集标识符为PXD 017158。结论：在我们的研究中，与血小板活化和伤口愈合相关的GP 6、PF 4和THBS 1在COPD患者中显著下调。这些结果表明，COPD患者更容易发生止血障碍，这可能会阻碍肺组织的修复过程。此外，CD 163、MARCO和VSIG 4的下调可能抑制炎症的消退并有助于COPD的发病机制，它们参与了肺泡巨噬细胞功能障碍。
Purpose: Chronic obstructive pulmonary disease (COPD) is a worldwide public health challenge due to its high prevalence and related disability and mortality; however, the pathogenesis of COPD remains unclear. In this study, we aimed to identify key proteins involved in the pathogenesis of COPD.Patients and Methods: We collected lung tissue from three patients with COPD who required thoracic surgery for lung transplantation in the China-Japan Friendship Hospital. Lung tissue from three donors who had no history of lung disease was collected as healthy controls through a whole-body donation program of Peking Union Medical College (China). We conducted a proteomic analysis of the protein expression profiles in the two groups using a combination of high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and quantitative 6-plex tandem mass tag-labeling; these data were validated by Western blot analysis.Results: A total of 4976 proteins were identified and analyzed, of which 173 were significantly changed (118 downregulated and 55 upregulated). Gene ontology analysis and protein-protein interaction networks demonstrated that the significantly changed proteins, especially downregulated proteins, were involved in platelet and macrophage activation. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (htty://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD017158.Conclusion: In our study, GP6, PF4, and THBS1, which are associated with platelet activation and wound healing, were significantly downregulated in COPD patients. These results indicate that patients with COPD are more likely to develop hemostasis disorders, which could impede the repair process of the lung tissues. Moreover, downregulation of CD163, MARCO and VSIG4, which are involved in dysfunction of alveolar macrophages in efferocytosis, may inhibit the resolution of inflammation and contribute to the pathogenesis of COPD.