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Int. J. Environ. Res. Public Health 2015, 12(9), 10739-10754; doi:10.3390/ijerph120910739

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

1
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China
2
College of Public Health, Tianjin Medical University, Tianjin 300070, China
3
Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang 110122, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 25 June 2015 / Revised: 18 August 2015 / Accepted: 25 August 2015 / Published: 1 September 2015
View Full-Text   |   Download PDF [8700 KB, uploaded 3 September 2015]   |  

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 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. View Full-Text
Keywords: silicosis; Wnt/β-catenin pathway; RNA interference; lentivirus; MMPs silicosis; Wnt/β-catenin pathway; RNA interference; lentivirus; MMPs
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MDPI and ACS Style

Wang, X.; Dai, W.; Wang, Y.; Gu, Q.; Yang, D.; Zhang, M. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice. Int. J. Environ. Res. Public Health 2015, 12, 10739-10754.

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