Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kneidinger, N; Yildirim, AO; Callegari, L; Takenaka, S; Stein, MM; Dumitrascu, R; Bohla, A; Bracke, KR; Morty, RE; Brusselle, GG; Schermuly, RT; Eickelberg, O; Königshoff, M.
Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema
AM J RESP CRIT CARE. 2011; 183(6): 723-733.
Doi: 10.1164/rccm.200910-1560OC
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Kneidinger Nikolaus
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- 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.
- Find related publications in this database (Keywords)
- chronic obstructive pulmonary disease
- emphysema
- WNT
- lung development