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Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema
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Journal Article
Activation of the WNT/β-Catenin Pathway Attenuates Experimental Emphysema
2011
Overview
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.
Publisher
American Thoracic Society
Subject
/ Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
/ Animals
/ Biological and medical sciences
/ Blood coagulation. Blood cells
/ Female
/ Fundamental and applied biological sciences. Psychology
/ General aspects, investigation methods, hemostasis, fibrinolysis
/ Humans
/ Male
/ Mice
/ Molecular and cellular biology
/ Pulmonary Disease, Chronic Obstructive - physiopathology
/ Pulmonary Emphysema - physiopathology
