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

ABSTRACT: 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.

SUBMITTER: Wang X 

PROVIDER: S-EPMC4586640 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature