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

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

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 he...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Medicine
R
Science
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Acceso en línea:https://doaj.org/article/910271cd28a0431e890028bbd9684f22
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Sumario: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.

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