Pengbo Sun1, Rui Ye1, Cuihong Wang1, Shuang Bai1, Li Zhao2. 1. Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. 2. Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. Electronic address: zhaol@sj-hospital.org.
Abstract
AIMS: Acute exacerbation is a major event that alters the natural course of chronic obstructive pulmonary disease (COPD), and recurrent exacerbation results in worse clinical outcomes and greater economic consequences. While some patients suffer frequent exacerbations, others experience no exacerbations; this study was designed to detect proteins that were differentially abundant in COPD frequent exacerbators and assess whether those expression profiles are unique among COPD patients. MAIN METHODS: Tandem mass tag labeled quantitative proteomics combined with two-dimensional liquid chromatography-tandem mass spectrometry was used to detect the changes in the lung proteome in COPD frequent exacerbators and infrequent exacerbators. A series of bioinformatics analyses were performed to screen potential signatures of COPD frequent exacerbations. The accuracy of proteomic results was further verified by western blot studies. KEY FINDINGS: Compared with infrequent exacerbators, 23 proteins in the lung tissues from frequent exacerbators showed significant degrees of differential expression; combined bioinformatics analyses of proteome indicated that the immune network for IgA production and the phenylalanine metabolism pathway were associated with frequent exacerbations. The Western blot analysis confirmed the expression pattern of three significantly regulated proteins (HLA-DQA1, pIgR and biglycan). SIGNIFICANCE: These findings indicate that immune response might play a key role in the pathophysiological mechanisms of COPD frequent exacerbations. Our results make a crucial contribution to the search for a comprehensive understanding of potential pathophysiological mechanisms associated with the frequent exacerbations of COPD, and might provide guidance for treating frequent exacerbations.
AIMS: Acute exacerbation is a major event that alters the natural course of chronic obstructive pulmonary disease (COPD), and recurrent exacerbation results in worse clinical outcomes and greater economic consequences. While some patients suffer frequent exacerbations, others experience no exacerbations; this study was designed to detect proteins that were differentially abundant in COPD frequent exacerbators and assess whether those expression profiles are unique among COPD patients. MAIN METHODS: Tandem mass tag labeled quantitative proteomics combined with two-dimensional liquid chromatography-tandem mass spectrometry was used to detect the changes in the lung proteome in COPD frequent exacerbators and infrequent exacerbators. A series of bioinformatics analyses were performed to screen potential signatures of COPD frequent exacerbations. The accuracy of proteomic results was further verified by western blot studies. KEY FINDINGS: Compared with infrequent exacerbators, 23 proteins in the lung tissues from frequent exacerbators showed significant degrees of differential expression; combined bioinformatics analyses of proteome indicated that the immune network for IgA production and the phenylalanine metabolism pathway were associated with frequent exacerbations. The Western blot analysis confirmed the expression pattern of three significantly regulated proteins (HLA-DQA1, pIgR and biglycan). SIGNIFICANCE: These findings indicate that immune response might play a key role in the pathophysiological mechanisms of COPD frequent exacerbations. Our results make a crucial contribution to the search for a comprehensive understanding of potential pathophysiological mechanisms associated with the frequent exacerbations of COPD, and might provide guidance for treating frequent exacerbations.
Authors: Haruhiko Furusawa; Jonathan H Cardwell; Tsukasa Okamoto; Avram D Walts; Iain R Konigsberg; Jonathan S Kurche; Tami J Bang; Marvin I Schwarz; Kevin K Brown; Jonathan A Kropski; Mauricio Rojas; Carlyne D Cool; Joyce S Lee; Paul J Wolters; Ivana V Yang; David A Schwartz Journal: Am J Respir Crit Care Med Date: 2020-11-15 Impact factor: 21.405
Authors: Yu-Hang Zhang; Michael R Hoopmann; Peter J Castaldi; Kirsten A Simonsen; Mukul K Midha; Michael H Cho; Gerard J Criner; Raphael Bueno; Jiangyuan Liu; Robert L Moritz; Edwin K Silverman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2021-10-20 Impact factor: 5.464