Dataset Information

PTPLAD2 and USP49 Involved in the Pathogenesis of Smoke-Induced COPD by Integrative Bioinformatics Analysis.

ABSTRACT: Purpose:Chronic obstructive pulmonary disease (COPD) is a typical chronic disease, but its molecular pathogenesis remains unclear. This study aimed to investigate the expression of biomarkers during COPD development. Methods:Markers significantly associated with COPD were screened using bioinformatics tools. qRT-PCR and Western blot were used to explore the expression of PTPLAD2 and USP49 in BEAS-2B cells. CCK-8 assay was used to determine the influence of PTPLAD2 and USP49 in BEAS-2B on cell proliferation. Results:In this study, 86 DEGs were identified in GSE76925. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that the phosphoinositide 3-kinase-Akt signaling pathway, ECM-receptor interaction, mRNA process, and viral transcription were all involved in the development of COPD. In addition, 14 hub genes were identified by WGCNA. PTPLAD2 and USP49 shared DEGs and hub genes and their expression levels were significantly reduced after CSE-treatment in BEAS-2B cells. Conclusion:Our results suggest that PTPLAD2 and USP49 may be useful biomarkers of COPD.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC7571584 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PTPLAD2 and USP49 Involved in the Pathogenesis of Smoke-Induced COPD by Integrative Bioinformatics Analysis.

Zhang Qiang Q Song Wei W Ayidaerhan Nahemuguli N He Zheng Z

International journal of chronic obstructive pulmonary disease 20201015

<h4>Purpose</h4>Chronic obstructive pulmonary disease (COPD) is a typical chronic disease, but its molecular pathogenesis remains unclear. This study aimed to investigate the expression of biomarkers during COPD development.<h4>Methods</h4>Markers significantly associated with COPD were screened using bioinformatics tools. qRT-PCR and Western blot were used to explore the expression of PTPLAD2 and USP49 in BEAS-2B cells. CCK-8 assay was used to determine the influence of PTPLAD2 and USP49 in BEA ...[more]

PMID: 33116468

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Project description:BackgroundCD147 is expressed in many tissues and is involved in many inflammatory diseases. Emerging evidence suggests that the overproduction of mucus is a malignant factor in chronic obstructive pulmonary disease (COPD), which results in severe airway obstruction and repeated airway infections. However, it is still unclear whether CD147 is involved in mucus production in COPD.MethodsWe determined the expression levels of CD147 and MUC5AC by immunohistochemistry in 42 human lung specimens from three groups (non-smokers without COPD, smokers without COPD and smokers with COPD). For the in vitro experiment, human bronchial epithelial (HBE) cells were treated with cigarette smoke (CS) extract to establish a mucus secretion model; then, CD147 and MUC5AC production were detected by RT-PCR, Western blotting and ELISA. To determine how CD147 is involved in MUC5AC secretion, HBE cells were transfected with small interfering RNA to silence CD147 and pretreated with inhibitors of MMP9 and p38 MAPK, which are common signaling molecules involved in MUC5AC secretion; then, MUC5AC expression was evaluated.ResultsCompared with the expression levels in the non-smokers and smokers without COPD, CD147 and MUC5AC expression levels were higher in the smokers with COPD. In the in vitro experiment, CD147 and MUC5AC expression levels were significantly increased after CS extract incubation compared with those after no treatment. Silencing CD147 by siRNA decreased the CS extract-induced MUC5AC secretion and MMP9 and phosphorylated p38 MAPK production. In addition, inhibiting MMP9 or p38 MAPK decreased the CS extract-induced MUC5AC secretion.ConclusionsIn lung specimens, CD147 and MUC5AC expression levels were increased in COPD patients. Increased CD147 levels induced by CS extract could stimulate MUC5AC secretion through the MMP9 and p38 MAPK signaling pathway in HBE cells. Therefore, the regulation of CD147 could be a promising target for mucus hypersecretion in COPD.

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Dataset Information

PTPLAD2 and USP49 Involved in the Pathogenesis of Smoke-Induced COPD by Integrative Bioinformatics Analysis.

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PTPLAD2 and USP49 Involved in the Pathogenesis of Smoke-Induced COPD by Integrative Bioinformatics Analysis.

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