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首页> 外文期刊>International Journal of Environmental Research and Public Health >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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Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

机译：慢病毒介导的靶向β-Catenin基因的短发夹RNA阻断Wnt /β-Catenin途径抑制小鼠的二氧化硅诱导的肺纤维化。

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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.
机译：矽肺病是由于吸入结晶硅尘而引起的一种职业性肺病。虽然尚不清楚矽肺的发病机理，但据认为Wnt /β-catenin信号通路在肺纤维化中起主要作用。为了探索Wnt /β-catenin途径在矽肺中的作用，我们通过使用慢病毒载体在二氧化硅处理的MLE-12细胞（小鼠肺上皮细胞系）和小鼠矽肺模型中均阻断了Wnt /β-catenin通路表达沉默β-catenin（Lv-shβ-catenin）的短发夹RNA。在体外，Lv-shβ-catenin显着降低了β-catenin，MMP2和MMP9的表达以及TGF-β1的分泌。在体内，气管内用Lv-shβ-catenin进行处理可显着降低肺中β-catenin的表达和支气管肺泡灌洗液中TGF-β1的水平，并显着减轻肺纤维化，这可通过硅胶中的羟脯氨酸含量和胶原I III合成证明给药的小鼠。这些结果表明，Wnt /β-catenin途径的阻断可以防止二氧化硅诱导的肺纤维化的发展。因此，Wnt /β-catenin途径可能是预防和治疗矽肺病的靶标。

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