Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Abstract

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.

A Species-Specific Strategy for the Identification of Hemocoagulase Agkistrodon halys pallas Based on LC-MS/MS-MRM

“…The database derived from transcriptome sequencing was used for the matching of MS/MS data and the proteomic assays were used for the verification of new protein sequences. The development of proteomics and genomics plays a key role in clinical diagnosis and treatment, identifying potential biomarkers, discovery of drug targets, and mechanisms of disease development ( Bai et al, 2021 ; Wang et al, 2021 ; Yang et al, 2021 ). In the global healthcare emergency caused by SARS-cov-2 since 2020, genomics, proteomics, and glycoproteomics have played a key role in the development of nucleic acid test kits, variant identification, vaccine development research, developing treatment options, studying infection mechanisms, and biomarkers’ investigation ( Alaiya et al, 2021 ; Wang L. et al, 2021 ).…”

Dehydrogenase reductase 9 (SDR9C4) and related homologs recognize a broad spectrum of lipid mediator oxylipins as substrates

“…Considering that human DHRS9 mRNA has a broad tissue distribution pattern ( 15 ), and the expression of DHRS9 is frequently altered during tissue inflammation and/or carcinogenesis as well as in metabolic disorders and obesity ( 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ), we reinvestigated the substrate specificity of human and rodent DHRS9. The results of this study suggest an evolutionarily conserved role for DHRS9 in the oxidative metabolism of a broad range of bioactive oxylipins.…”