• Harikrishna Tanjore, Amber L Degryse, Peter F Crossno, Xiaochuan C Xu, Melinda E McConaha, Brittany R Jones, Vasiliy V Polosukhin, Andrew J Bryant, Dong-Sheng Cheng, Dawn C Newcomb, Frank B McMahon, Linda A Gleaves, Timothy S Blackwell, and William E Lawson.
• Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232-2650, USA.
• Am. J. Respir. Crit. Care Med. 2013 Mar 15; 187 (6): 630-9.

RationaleAlveolar epithelial cells (AECs) play central roles in the response to lung injury and the pathogenesis of pulmonary fibrosis.ObjectivesWe aimed to determine the role of β-catenin in alveolar epithelium during bleomycin-induced lung fibrosis.MethodsGenetically modified mice were developed to selectively delete β-catenin in AECs and were crossed to cell fate reporter mice that express β-galactosidase (βgal) in cells of AEC lineage. Mice were given intratracheal bleomycin (0.04 units) and assessed for AEC death, inflammation, lung injury, and fibrotic remodeling. Mouse lung epithelial cells (MLE12) with small interfering RNA knockdown of β-catenin underwent evaluation for wound closure, proliferation, and bleomycin-induced cytotoxicity.Measurements And Main ResultsIncreased β-catenin expression was noted in lung parenchyma after bleomycin. Mice with selective deletion of β-catenin in AECs had greater AEC death at 1 week after bleomycin, followed by increased numbers of fibroblasts and enhanced lung fibrosis as determined by semiquantitative histological scoring and total collagen content. However, no differences in lung inflammation or protein levels in bronchoalveolar lavage were noted. In vitro, β-catenin-deficient AECs showed increased bleomycin-induced cytotoxicity as well as reduced proliferation and impaired wound closure. Consistent with these findings, mice with AEC β-catenin deficiency showed delayed recovery after bleomycin.Conclusionsβ-Catenin in the alveolar epithelium protects against bleomycin-induced fibrosis. Our studies suggest that AEC survival and wound healing are enhanced through β-catenin-dependent mechanisms. Activation of the developmentally important β-catenin pathway in AECs appears to contribute to epithelial repair after epithelial injury.

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