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Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes

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dc.contributor.author Esteve-Codina, Anna
dc.contributor.author Soler Artigas, María
dc.contributor.author Dabad, Marc
dc.contributor.author Fernández Callejo, Marcos
dc.contributor.author Griebel, Thasso
dc.contributor.author Heath, Simon
dc.contributor.author Gut, Ivo Glynne
dc.contributor.author Ziegler-Heitbrock, Loems
dc.date.accessioned 2021-11-25T06:51:34Z
dc.date.available 2021-11-25T06:51:34Z
dc.date.issued 2021
dc.identifier.citation Esteve-Codina A, Hofer TP, Burggraf D, Heiss-Neumann MS, Gesierich W, Boland A et al. Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes. Sci Rep. 2021;11(1):12848. DOI: 10.1038/s41598-021-91742-x
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/49051
dc.description.abstract Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.
dc.description.sponsorship This work was supported by the European Union, FP7 project # 200506. We acknowledge the helpful discussions with Emanuele Raineri, Barcelona, Spain and with Wilfried Karmaus, Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tennessee, USA. CNAG-CRG lab is a member of the Spanish National Bioinformatics Institute (INB), PRB2-ISCIII and is supported by grant PT13/0001 of the PE I+D+i 2013-2016, funded by ISCIII and FEDER. Work by CB at Leicester and by LZH at Munich was also supported the European Union FP7 project # 270194.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Sci Rep. 2021;11(1):12848
dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-91742-x
dc.subject.keyword Immunology
dc.subject.keyword Medical research
dc.subject.keyword Molecular biology
dc.subject.keyword Molecular medicine
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/270194
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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