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KNEIDINGER, Nikolaus; ONDER YILDIRIM, Ali; THEO SCHERMULY, Ralph; EICKELBERG, Oliver; KÖNIGSHOFF, Melanie; CALLEGARI, Jens; TAKENAKA, Shinji; MAGDALENA STEIN, Maria; DUMITRASCU, Rio; BOHIA, Alexander; BRACKE, Ken R; MORTY, Rory E; BRUSSELLE, Guy G
American journal of respiratory and critical care medicine, 03/2011, Letnik: 183, Številka: 6Journal Article
Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available. 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. The expression, localization, and activity of WNT/β-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/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. 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 β-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/β-catenin signaling was down-regulated in both experimental emphysema models. Preventive and 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. 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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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