Esteve-Codina, A.* ; Hofer, T.P. ; Burggraf, D. ; Heiss-Neumann, M.S. ; Gesierich, W. ; Boland, A.* ; Olaso, R.* ; Bihoreau, M.T.* ; Deleuze, J.F.* ; Möller, W. ; Schmid, O. ; Soler Artigas, M.* ; Renner, K.* ; Hohlfeld, J.M.* ; Welte, T.* ; Fuehner, T.* ; Jerrentrup, L.* ; Koczulla, A.R.* ; Greulich, T.* ; Prasse, A.* ; Müller-Quernheim, J.* ; Gupta, S.* ; Brightling, C.* ; Subramanian, D.R.* ; Parr, D.G.* ; Kolsum, U.* ; Gupta, V.* ; Barta, I.* ; Döme, B.* ; Strausz, J.* ; Stendardo, M.* ; Piattella, M.* ; Boschetto, P.* ; Korzybski, D.* ; Gorecka, D.* ; Nowinski, A.* ; Dabad, M.* ; Fernández-Callejo, M.* ; Endesfelder, D. ; zu Castell, W. ; Hiemstra, P.S.* ; Venge, P.* ; Nößner, E. ; Griebel, T.* ; Heath, S.* ; Singh, D.* ; Gut, I.* ; Ziegler-Heitbrock, L.
Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes.
Sci. Rep. 11:12848 (2021)
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.
Impact Factor
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Times Cited
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Cited By
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Obstructive Pulmonary-disease; Oxidative Stress; Gro-alpha; Emphysema; Epithelium
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
2045-2322
e-ISSN
2045-2322
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 11,
Heft: 1,
Seiten: ,
Artikelnummer: 12848
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
30503 - Chronic Diseases of the Lung and Allergies
30202 - Environmental Health
30505 - New Technologies for Biomedical Discoveries
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Immune Response and Infection
Lung Research
Enabling and Novel Technologies
PSP-Element(e)
G-502710-001
G-501690-001
G-505000-008
G-503890-001
G-505900-001
Förderungen
European Commission
Copyright
Erfassungsdatum
2021-06-28