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.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.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.doi http://dx.doi.org/10.1038/s41598-021-91742-x
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/49051
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Sci Rep. 2021;11(1):12848
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/270194
• 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Immunology
• dc.subject.keyword Medical research
• dc.subject.keyword Molecular biology
• dc.subject.keyword Molecular medicine
• 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.type.version info:eu-repo/semantics/publishedVersion