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Kneidinger, N.* ; Yildirim, A.Ö. ; Callegari, J. ; Takenaka, S. ; Stein, M.M. ; Dumitrascu, R.* ; Bohla, A. ; Bracke, K.R.* ; Morty, R.E.* ; Brusselle, G.G.* ; Schermuly, R.T.* ; Eickelberg, O. ; Königshoff, M.

Activation of the WNT/β-catenin pathway attenuates experimental emphysema.

Am. J. Respir. Crit. Care Med. 183, 723-733 (2011)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
RATIONALE: Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available. OBJECTIVES: To characterize WNT/β-catenin signaling in COPD in humans and elucidate its potential role as a preventive and therapeutic target in experimental emphysema in mice. METHODS: The expression, localization, and activity of WNT/β-catenin signaling was assessed in 12 COPD and 12 transplant donor samples using quantitative RT-PCR, immunohistochemistry, and Western blotting. The role of WNT/β-catenin signaling was assessed in elastase- and cigarette smoke-induced emphysema and therapeutic modulation thereof in elastase-induced emphysema in TOPGAL reporter and wild type mice in vivo. MEASUREMENTS AND MAIN RESULTS: No differences in the mRNA expression profile of the main WNT/β-catenin signaling components were observed comparing COPD and donor lung homogenates. Immunohistochemical analysis revealed reduced numbers of nuclear !-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/β-catenin signaling was downregulated in both experimental emphysema models. Preventive, as well as therapeutic, WNT/β-catenin activation by lithium chloride attenuated experimental emphysema, as assessed by decreased airspace enlargement, improved lung function, reduced collagen content, and elevated expression of alveolar epithelial cell markers. CONCLUSION: Decreased WNT/β-catenin signaling is involved in parenchymal tissue destruction and impaired repair capacity in emphysema. These data indicate a crucial role of WNT/β-catenin signaling in lung repair mechanisms in vivo, and highlight WNT/β-catenin activation as a future therapeutic approach for emphysema.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter COPD; emphysema; WNT; lung development
Sprache
Veröffentlichungsjahr 2011
Prepublished im Jahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Zeitschrift American Journal of Respiratory and Critical Care Medicine
Quellenangaben Band: 183, Heft: 6, Seiten: 723-733 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Lung Research
PSP-Element(e) G-501600-001
PubMed ID 20889911
DOI 10.1164/rccm.200910-1560OC
WOS ID WOS:000288970600009
Erfassungsdatum 2010-12-31
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