Localization pattern of β-catenin in chronic lung disease

Abstract

Rationale: The WNT/β-catenin signaling has been recently demonstrated to be involved in lung epithelial injury and repair processes. Nuclear localization of β-catenin is a surrogate marker of WNT/β-catenin activation in human tissue. Here, we investigated in detail the distribution pattern of WNT/β-catenin in human tissue specimen obtained from patients with chronic lung diseases. Methods and Results: By means of double immunohistochemical staining of β-catenin and surfactant protein C (SP-C), localization of β-catenin in alveolar epithelial type II (ATII) cells was examined in tissue samples obtained from lung fibrosis or emphysema patients, and control subjects (transplant donors). Highest level of nuclear β-catenin was observed in hyperplastic ATII cells in fibrotic lung tissue (66.1±4.1%), while control lungs exhibited moderate nuclear localization of β-catenin in ATII cells (24.2±11%). Interestingly, β-catenin-positive cells were mainly observed in preserved alveolar structure in lung fibrosis. In the honeycombing lesion, which showed cystically dilated lumens lined by columnar epithelia, a few SP-C positive cells were found and the cells showed frequent nuclear localization of β-catenin. In contrast, in emphysematous tissue samples, a low incidence of nuclear localization was found (4.7±1.5%). Conclusion: Activation of WNT/β-catenin signaling in ATII cells, as assessed by nuclear β-catenin, may serve as a marker for alveolar epithelial cell activation in chronic lung disease.