International Journal of COPD (May 2020)
Proteome Profiling of Lung Tissues in Chronic Obstructive Pulmonary Disease (COPD): Platelet and Macrophage Dysfunction Contribute to the Pathogenesis of COPD
Abstract
Yifan Liu,1,2,* Haotian Liu,3,* Chunyuan Li,3 Chao Ma,1,2 Wei Ge3 1Institute of Basic Medical Sciences, Neuroscience Center, National Human Brain Bank for Development and Function, Chinese Academy of Medical Sciences, Beijing 100005, People’s Republic of China; 2Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, People’s Republic of China; 3State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Ge; Chao Ma Email [email protected]; [email protected]: 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 (http://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.Keywords: chronic obstructive pulmonary disease, proteomics, macrophage, platelet
