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β-Catenin Is Not Necessary for Maintenance or Repair of the Bronchiolar Epithelium

¹ Center for Lung Regeneration, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania; and ² Division of Pulmonary and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina

Correspondence and requests for reprints should be addressed to Barry R. Stripp, Ph.D., Duke University Medical Center, 2075 MSRBII, 106 Research Drive, DUMC Box 103000, Durham, NC 27710. E-mail: barry.stripp{at}duke.edu.

Signaling by Wnt/β-catenin regulates self-renewal of tissue stem cells in the gut and, when activated in the embryonic bronchiolar epithelium, leads to stem cell expansion. We have used transgenic and cell type–specific knockout strategies to determine roles for β-catenin–regulated gene expression in normal maintenance and repair of the bronchiolar epithelium. Analysis of TOPGal transgene activity detected β-catenin signaling in the steady-state and repairing bronchiolar epithelium. However, the broad distribution and phenotype of signaling cells precluded establishment of a clear role for β-catenin in the normal or repairing state. Necessity of β-catenin signaling was tested through Cre-mediated deletion of Catnb exons 2–6 in airway epithelial cells. Functional knockout of β-catenin had no impact on expression of Clara cell differentiation markers, mitotic index, or sensitivity of these cells to the Clara cell–specific toxicant, naphthalene. Repair of the naphthalene-injured airway proceeded with establishment of focal regions of β-catenin–null epithelium. The size of regenerative epithelial units, mitotic index, and restoration of the ciliated cell population did not vary between wild-type and genetically modified mice. Thus, β-catenin was not necessary for maintenance or efficient repair of the bronchiolar epithelium.

Key Words: injury • repair • β-catenin • progenitor

CLINICAL RELEVANCE These studies help define signaling pathways that regulate airway repair and might be exploited to manipulate epithelial repair capacity.

 

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