Scientific Reports (Jun 2021)
Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes
- Anna Esteve-Codina,
- Thomas P. Hofer,
- Dorothe Burggraf,
- Marion S. Heiss-Neumann,
- Wolfgang Gesierich,
- Anne Boland,
- Robert Olaso,
- Marie-Therese Bihoreau,
- Jean-Francois Deleuze,
- Winfried Moeller,
- Otmar Schmid,
- María Soler Artigas,
- Kathrin Renner,
- Jens M. Hohlfeld,
- Tobias Welte,
- Thomas Fuehner,
- Lukas Jerrentrup,
- Andreas Rembert Koczulla,
- Timm Greulich,
- Antje Prasse,
- Joachim Müller-Quernheim,
- Sumit Gupta,
- Christopher Brightling,
- Deepak R. Subramanian,
- David G. Parr,
- Umme Kolsum,
- Vandana Gupta,
- Imre Barta,
- Balázs Döme,
- János Strausz,
- Mariarita Stendardo,
- Marco Piattella,
- Piera Boschetto,
- Damian Korzybski,
- Dorota Gorecka,
- Adam Nowinski,
- Marc Dabad,
- Marcos Fernández-Callejo,
- David Endesfelder,
- Wolfgang zu Castell,
- Pieter S. Hiemstra,
- Per Venge,
- Elfriede Noessner,
- Thasso Griebel,
- Simon Heath,
- Dave Singh,
- Ivo Gut,
- Loems Ziegler-Heitbrock
Affiliations
- Anna Esteve-Codina
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Thomas P. Hofer
- EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik
- Dorothe Burggraf
- EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik
- Marion S. Heiss-Neumann
- EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik
- Wolfgang Gesierich
- EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik
- Anne Boland
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay
- Robert Olaso
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay
- Marie-Therese Bihoreau
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay
- Jean-Francois Deleuze
- Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay
- Winfried Moeller
- Institute for Lung Biology and Disease, Helmholtz Zentrum Muenchen
- Otmar Schmid
- Institute for Lung Biology and Disease, Helmholtz Zentrum Muenchen
- María Soler Artigas
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Kathrin Renner
- Internal Medicine III, University Hospital Regensburg
- Jens M. Hohlfeld
- Fraunhofer Institute for Toxicology and Experimental Medicine
- Tobias Welte
- Department of Respiratory Medicine, Hannover Medical School
- Thomas Fuehner
- Department of Respiratory Medicine, Hannover Medical School
- Lukas Jerrentrup
- Member of the German Center for Lung Research (DZL)
- Andreas Rembert Koczulla
- Member of the German Center for Lung Research (DZL)
- Timm Greulich
- Member of the German Center for Lung Research (DZL)
- Antje Prasse
- Fraunhofer Institute for Toxicology and Experimental Medicine
- Joachim Müller-Quernheim
- Department of Pneumology, Faculty of Medicine, University of Freiburg
- Sumit Gupta
- Institute for Lung Health, NIHR Leicester BRC, University of Leicester
- Christopher Brightling
- Institute for Lung Health, NIHR Leicester BRC, University of Leicester
- Deepak R. Subramanian
- Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust
- David G. Parr
- Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust
- Umme Kolsum
- Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester Foundations Trust
- Vandana Gupta
- Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester Foundations Trust
- Imre Barta
- Department of Pathophysiology, National Koranyi Institute for TB and Pulmonology
- Balázs Döme
- Department of Tumorbiology, National Koranyi Institute for TB and Pulmonology
- János Strausz
- Department of Pneumology, National Koranyi Institute for TB and Pulmonology
- Mariarita Stendardo
- Department of Medical Sciences, University of Ferrara and Ferrara City Hospital
- Marco Piattella
- Department of Medical Sciences, University of Ferrara and Ferrara City Hospital
- Piera Boschetto
- Department of Medical Sciences, University of Ferrara and Ferrara City Hospital
- Damian Korzybski
- 2nd Department of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases
- Dorota Gorecka
- 2nd Department of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases
- Adam Nowinski
- 2nd Department of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases
- Marc Dabad
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Marcos Fernández-Callejo
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- David Endesfelder
- ICT Department, Helmholtz Zentrum Muenchen
- Wolfgang zu Castell
- Department Strategy & Digitalization, Helmholtz Zentrum Muenchen
- Pieter S. Hiemstra
- Department of Pulmonology, Leiden University Medical Center
- Per Venge
- Department of Medical Sciences, University of Uppsala
- Elfriede Noessner
- Immunoanalytics-Tissue Control of Immunocytes, Helmholtz Zentrum Muenchen
- Thasso Griebel
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Simon Heath
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Dave Singh
- Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester Foundations Trust
- Ivo Gut
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)
- Loems Ziegler-Heitbrock
- EvA Study Center, Helmholtz Zentrum Muenchen and Asklepios-Klinik
- DOI
- https://doi.org/10.1038/s41598-021-91742-x
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
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.
