Pneumologie 2011; 65 - A11
DOI: 10.1055/s-0031-1296102

Activation of Wnt/β-catenin signaling promotes lung epithelial repair

J Callegari 1, N Kneidinger 1, J Kipp 1, M Königshoff 1
  • 1Comprehensive Pneumology Center, Ludwig-Maximilians-University, Asklepios Hospital, and Helmholtz Zentrum München

Background: Pulmonary emphysema is characterized by airspace enlargement and impaired alveolar repair capacity. Recently, we reported that the Wnt/β-catenin pathway represent as a potential target to promote survival and repair of alveolar epithelial cells in emphysema.

Aim: To elucidate Wnt/β-catenin signaling activity in murine pulmonary emphysema and response of primary alveolar epithelial cells upon Wnt/β-catenin activation.

Methods: Wnt/β-catenin reporter mice (TOPGAL), carrying the lacZ gene under control of Lef/Tcf-binding motifs upstream of a minimal c-fos promoter, were used to induce emphysema by elastase instillation (ot) and subsequently treated with lithium chloride (LiCl) (ip) to activate Wnt/β-catenin signaling. The β-galactosidase and nuclear β-catenin staining was assessed by immunohistochemistry. Further, alveolar epithelial type II (ATII) cells were isolated from elastase treated mice and gene expression was analysed by qRT-PCR. Further, the effects of Wnt3a on primary ATII cell cultures were investigated by qRT-PCR and immunofluorescence. Cell proliferation was analyzed by BrdU incorporation assay.

Results: Primary ATII cells isolated from elastase-treated mice demonstrated reduced activity of the Wnt/β-catenin pathway, as determined by expression of target genes, such as Axin2 and Lef1. Wnt/β-catenin activation by LiCl demonstrated increased β-galactosidase staining and nuclear β-catenin in SPC-positive alveolar epithelial cells in experimental emphysema in vivo. Importantly, Wnt/β-catenin activation led to elevated expression of alveolar epithelial cell marker in vivo. Wnt3a stimulation of primary ATII cells in vitro revealed an increased expression of Wnt target genes, epithelial cell marker tight junction protein 1 and occludin as well as increased proliferation.

Conclusion: Wnt/β-catenin activation promotes increased repair capacity of alveolar epithelial type II cells in vitro and in vivo. Hence, Wnt/β-catenin signaling might be a useful therapeutic target in pulmonary emphysema.