Identification of proteomic signatures associated with COPD frequent exacerbators

Sun, Pengbo; Rui, Yong; Wang, Cuihong; Bai, Shuang; Zhao, Li

doi:10.1016/j.lfs.2019.05.047

Cited by 15 publications

(14 citation statements)

References 30 publications

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“…Of these, 25 DAPs were upregulated and 11 DAPs were downregulated. This result was comparable with that of other proteomic analyses on lung tissue ( Sun et al, 2019 ; Wu et al, 2020 ). Functional enrichment analysis of DAPs showed that tissue repair and cell proliferation and development were primarily related to the pathogenesis of emphysematous phenotype, in addition to inflammatory response, collagen disruption, and other well-recognized mechanisms in emphysema ( Lan et al, 2019 ).…”

Section: Discussionsupporting

confidence: 91%

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Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Bai

Rui

Wang

et al. 2021

Front. Mol. Biosci.

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Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease. Emphysematous phenotype is the most common and critical phenotype, which is characterized by progressive lung destruction and poor prognosis. However, the underlying mechanism of this structural damage has not been completely elucidated. A total of 12 patients with COPD emphysematous phenotype (COPD-E) and nine patients with COPD non-emphysematous phenotype (COPD-NE) were enrolled to determine differences in differential abundant protein (DAP) expression between both groups. Quantitative tandem mass tag–based proteomics was performed on lung tissue samples of all patients. A total of 29 and 15 lung tissue samples from patients in COPD-E and COPD-NE groups, respectively, were used as the validation cohort to verify the proteomic analysis results using western blotting. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted for DAPs. A total of 4,343 proteins were identified, of which 25 were upregulated and 11 were downregulated in the COPD-E group. GO and KEGG analyses showed that wound repair and retinol metabolism–related pathways play an essential role in the molecular mechanism of COPD emphysematous phenotype. Three proteins, namely, KRT17, DHRS9, and FMO3, were selected for validation. While KRT17 and DHRS9 were highly expressed in the lung tissue samples of the COPD-E group, FMO3 expression was not significantly different between both groups. In conclusion, KRT17 and DHRS9 are highly expressed in the lung tissue of patients with COPD emphysematous phenotype. Therefore, these proteins might involve in wound healing and retinol metabolism in patients with emphysematous phenotype and can be used as phenotype-specific markers.

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Section: Discussionsupporting

confidence: 91%

“…Samples were prepared as described previously ( Sun et al, 2019 ; Bai et al, 2020 ). In brief, lung tissue samples were obtained as far as possible from the tumor (at least 5 cm from the boundary).…”

Section: Methodsmentioning

confidence: 99%

Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Bai

Rui

Wang

et al. 2021

Front. Mol. Biosci.

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“…These individuals have high levels of inflammatory cytokines such as interleukin-6 in sputum (Bhowmik et al, 2000), and show a high risk of adverse health outcomes. In our previous study on patients with frequent COPD exacerbations, proteomics analysis showed low expression of several proteins in lung tissues (Sun et al, 2019). Moreover, AGR3 was significantly decreased and previous study (Bonser et al, 2015) showed AGR3 expressed in the respiratory airway epithelium.…”

Section: Discussionmentioning

confidence: 72%

“…The underlying mechanisms and predisposing factors of the frequentexacerbation COPD phenotype are still unclear. A previous study on the proteomics of lung tissues in patients with frequent COPD exacerbations identified 23 differentially expressed proteins (Sun et al, 2019), including anterior gradient 3 (AGR3).…”

Section: Introductionmentioning

confidence: 99%

AGR3 Regulates Airway Epithelial Junctions in Patients with Frequent Exacerbations of COPD

Wang

Sun

et al. 2021

Front. Pharmacol.

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Background: The mechanisms underlying differences in the susceptibility to chronic obstructive pulmonary disease (COPD) exacerbations between patients are not well understood. Recent studies have shown that the patients with frequent COPD exacerbations is related to specific protein expression in lung tissue. Anterior gradient 3 (AGR3) is expressed in airway epithelial cells in the lung and proteomic analysis revealed that its expression is decreased in patients with frequent COPD exacerbations. Moreover, the loss of epithelial integrity might facilitate trans-epithelial permeability of pathogens in such patients. This study was performed to determine that AGR3 protein play a role in COPD frequency exacerbators.Methods: Human lung tissues were collected from current-smoking patients (Control; n = 15) as well as patients with infrequent COPD exacerbations (IFCOPD; n = 18) and frequent COPD exacerbations (FCOPD; n = 8). While AGR3 protein expression was measured by immunohistochemistry and western blotting, AGR mRNA expression was determined by real time quantitative polymerase chain reaction (RT-qPCR). Furthermore, adherent junctions (AJs) and tight junctions (TJs) protein expression in human lung tissues were measured by immunohistochemistry. The effects of cigarette smoke extract (CSE) on AJ and TJ protein and mRNA expression in BEAS-2B cells were assessed by western blotting and RT-qPCR. In addition, the effect of AGR3 overexpression and knockdown on AJ and TJ protein expression was determined.Results: AGR3 was mainly expressed in the airway epithelium and AGR3-positive products were localized in the cytoplasm. Western blotting and RT-qPCR results showed that AGR3 protein (p = 0.009) and mRNA (p = 0.04) expression in the FCOPD group was significantly lower than that in the IFCOPD group. Moreover, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression was lower in the FCOPD group than in the IFCOPD group. The protein and mRNA expression of E-cadherin, occludin, and ZO-1 was decreased within 24 h post-CSE exposure. AGR3 overexpression rescued CSE-induced downregulation of E-cadherin, occludin, and ZO-1.Conclusion: Difference in AGR3 expression in the lung tissue might be correlated with increased susceptibility to COPD exacerbation. AGR3 can prevent CSE-induced downregulation of E-cadherin, occludin, and ZO-1 in airway epithelial cells. Loss of AGR3 might promote viral and bacterial infection and induce immune inflammation to increase COPD exacerbation.

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“…Frequent exacerbations are the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype [84][85][86][87] . Therefore, reduction of AEs has beneficial impact on patient outcomes and prognosis 81,88 .…”

Section: Frequent Exacerbator Phenotypementioning

confidence: 99%

Chronic obstructive pulmonary disease - diagnosis and management of stable disease; a personalized approach to care, using the treatable traits concept based on clinical phenotypes. Position paper of the Czech Pneumological and Phthisiological Society

et al. 2020

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Identification of proteomic signatures associated with COPD frequent exacerbators

Cited by 15 publications

References 30 publications

Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

AGR3 Regulates Airway Epithelial Junctions in Patients with Frequent Exacerbations of COPD

Chronic obstructive pulmonary disease - diagnosis and management of stable disease; a personalized approach to care, using the treatable traits concept based on clinical phenotypes. Position paper of the Czech Pneumological and Phthisiological Society

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