Blocking the Wnt/β-catenin pathway by lentivirus-mediated short hairpin RNA targeting β-catenin gene suppresses silica-induced lung fibrosis in mice

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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.

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Wang, X., Dai, W., Wang, Y., Gu, Q., Yang, D., & Zhang, M. (2015). Blocking the Wnt/β-catenin pathway by lentivirus-mediated short hairpin RNA targeting β-catenin gene suppresses silica-induced lung fibrosis in mice. International Journal of Environmental Research and Public Health, 12(9), 10739–10754. https://doi.org/10.3390/ijerph120910739

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