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

Xin Wang, Wujing Dai, Yanrang Wang, Qing Gu, Deyi Yang and Ming Zhang
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Xin Wang: Tianjin Center for Disease Control and Prevention, Tianjin 300011, China
Wujing Dai: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang 110122, China
Yanrang Wang: Tianjin Center for Disease Control and Prevention, Tianjin 300011, China
Qing Gu: Tianjin Center for Disease Control and Prevention, Tianjin 300011, China
Deyi Yang: Tianjin Center for Disease Control and Prevention, Tianjin 300011, China
Ming Zhang: Tianjin Center for Disease Control and Prevention, Tianjin 300011, China

IJERPH, 2015, vol. 12, issue 9, 1-16

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/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 IIII 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.

Keywords: silicosis; Wnt/β-catenin pathway; RNA interference; lentivirus; MMPs (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2015
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