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.
Highlights
Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust [1,2].the pathogenesis of silicosis is not clearly understood
To examine the effects of Lv-shβ-catenin on expression of β-catenin, MMP2, and MMP9, and secretion of transforming growth factor-β1 (TGF-β1) in the silica-treated MLE-12 cells, real-time PCR, western blot and ELISA assays were performed (Figure 2).The results showed that Lv-shβ-catenin significantly suppressed β-catenin mRNA and protein expression in cells activated by silica (Figure 2A,D)
As matrix metalloproteinases (MMPs) play important roles in the pathogenesis of silicosis, we examined the expression of MMP2 and MMP9 in silica-treated MLE-12 cells
Summary
Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust [1,2].the pathogenesis of silicosis is not clearly understood. Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust [1,2]. The Wnt/β-catenin signaling pathway participates in development, regeneration, and remodeling of the lung. Dysregulation of Wnt/β-catenin signaling results in various diseases of lung tissue, such as lung cancer and idiopathic pulmonary fibrosis [3,4]. Recent studies have suggested that the Wnt/β-catenin signaling pathway plays an important role in pulmonary fibrosis [5,6], which is a typical pathological characteristic in silicosis. The Wnt signaling pathway is highly conserved in evolution. It can be divided into three distinct pathways, and the “canonical” β-catenin dependent Wnt signaling pathway is best characterized [7,8]
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