Esteve-Codina, Anna and Hofer, Thomas P. and Burggraf, Dorothe and Heiss-Neumann, Marion S. and Gesierich, Wolfgang and Boland, Anne and Olaso, Robert and Bihoreau, Marie-Therese and Deleuze, Jean-Francois and Moeller, Winfried and Schmid, Otmar and Artigas, Maria Soler and Renner, Kathrin and Hohlfeld, Jens M. and Welte, Tobias and Fuehner, Thomas and Jerrentrup, Lukas and Koczulla, Andreas Rembert and Greulich, Timm and Prasse, Antje and Mueller-Quernheim, Joachim and Gupta, Sumit and Brightling, Christopher and Subramanian, Deepak R. and Parr, David G. and Kolsum, Umme and Gupta, Vandana and Barta, Imre and Dome, Balazs and Strausz, Janos and Stendardo, Mariarita and Piattella, Marco and Boschetto, Piera and Korzybski, Damian and Gorecka, Dorota and Nowinski, Adam and Dabad, Marc and Fernandez-Callejo, Marcos and Endesfelder, David and zu Castell, Wolfgang and Hiemstra, Pieter S. and Venge, Per and Noessner, Elfriede and Griebel, Thasso and Heath, Simon and Singh, Dave and Gut, Ivo and Ziegler-Heitbrock, Loems (2021) Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes. SCIENTIFIC REPORTS, 11 (1): 12848. ISSN 2045-2322
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OBSTRUCTIVE PULMONARY-DISEASE; OXIDATIVE STRESS; GRO-ALPHA; EMPHYSEMA; EPITHELIUM |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Sep 2022 05:06 |
| Last Modified: | 14 Sep 2022 05:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48152 |
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