Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/-catenin pathway in silicosis, we blocked Wnt/-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing -catenin (Lv-sh-catenin). In vitro, Lv-sh-catenin significantly decreased the expression of -catenin, MMP2 and MMP9, and secretion of TGF-1. In vivo, intratracheal treatment with Lv-sh-catenin significantly reduced expression of -catenin in the lung and levels of TGF-1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/-catenin pathway may be a target in prevention and treatment of silicosis.