Journalartikel

Jahr der Veröffentlichung: 2011

Seiten: 723-733

Zeitschrift: American Journal of Respiratory and Critical Care Medicine

Bandnummer: 183

Heftnummer: 6

ISSN: 1073-449X

eISSN: 1535-4970

DOI Link: https://doi.org/10.1164/rccm.200910-1560OC

Verlag: American Thoracic Society

Abstract: 

Rationale: Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available.

Objectives: To characterize WNT/beta-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/beta-catenin signaling was assessed in 12 COPD and 12 transplant donor samples using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and Western blotting. The role of WNT/beta-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/beta-catenin signaling components were observed comparing COPD and donor lung homogenates. Immunohistochemical analysis revealed reduced numbers of nuclear beta-catenin positive alveolar epithelial cells in COPD. Similarly, WNT/beta-catenin signaling was down-regulated in both experimental emphysema models. Preventive and therapeutic, WNT/beta-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.

Conclusions: Decreased WNT/beta-catenin signaling is involved in parenchymal tissue destruction and impaired repair capacity in emphysema. These data indicate a crucial role of WNT/beta-catenin signaling in lung repair mechanisms in vivo, and highlight WNT/beta-catenin activation as a future therapeutic approach for emphysema.

Harvard-Zitierstil: Kneidinger, N., Yildirim, A., Callegari, L., Takenaka, S., Stein, M., Dumitrascu, R., et al. (2011) Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema, American Journal of Respiratory and Critical Care Medicine, 183(6), pp. 723-733. https://doi.org/10.1164/rccm.200910-1560OC

APA-Zitierstil: Kneidinger, N., Yildirim, A., Callegari, L., Takenaka, S., Stein, M., Dumitrascu, R., Bohla, A., Bracke, K., Morty, R., Brusselle, G., Schermuly, R., Eickelberg, O., & Koenigshoff, M. (2011). Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema. American Journal of Respiratory and Critical Care Medicine. 183(6), 723-733. https://doi.org/10.1164/rccm.200910-1560OC