Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice.
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.
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China. h_angel@126.com.|College of Public Health, Tianjin Medical University, Tianjin 300070, China. h_angel@126.com.
Xin
X
Wang
Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang 110122, China. wujingDai2012@126.com.
Wujing
W
Dai
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China. wangyanrang2014@126.com.
Yanrang
Y
Wang
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China. qinggu1118@126.com.
Qing
Q
Gu
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China. yangdeyi2013@163.com.
Deyi
D
Yang
Tianjin Center for Disease Control and Prevention, Tianjin 300011, China. zhangming0124@yeah.net.
Ming
M
Zhang
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D004195:Disease Models, Animal; D020868:Gene Silencing / Q000502:physiology; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000517:prevention & control*; D034741:RNA, Small Interfering / Q000235:genetics*; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000378:metabolism / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D012822:Silicon Dioxide; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
MMPs; RNA interference; Wnt/β-catenin pathway; lentivirus; silicosis