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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 559760.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Activation of the WNT/{beta}-Catenin Pathway Attenuates Experimental Emphysema
Authors:Kneidinger, N.; Yildirim, A. O.; 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.; Konigshoff, M.
Title of Journal:Am J Respir Crit Care Med
Audience:Not Specified
Abstract / Description: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 RT-PCR, 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 !-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/beta-catenin signaling was downregulated in both experimental emphysema models. Preventive, as well as 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. CONCLUSION: 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.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Medicine, University of Giessen Lung Center, University of Giessen, Giessen, Germany.
Identifiers:ISSN:1535-4970 (Electronic) 1073-449X (Linking)
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