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

• Published in: International journal of environmental research and public health Vol. 12; no. 9; p. 10739
• Main Authors: Wang, Xin, Dai, Wujing, Wang, Yanrang, Gu, Qing, Yang, Deyi, Zhang, Ming
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2015
• Subjects: Genes; Lung diseases; Ribonucleic acid; RNA; Silica
• ISSN: 1661-7827; 1660-4601

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/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-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 β-catenin (Lv-shβ-catenin). In vitro, Lv-shβ-catenin significantly decreased the expression of β-catenin, MMP2 and MMP9, and secretion of TGF-β1. In vivo, intratracheal treatment with Lv-shβ-catenin significantly reduced expression of β-catenin in the lung and levels of TGF-β1 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/β-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/β-catenin pathway may be a target in prevention and treatment of silicosis.