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
Xin WangMing Zhang

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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Citations

Apr 12, 2016·Stem Cells International·Miquéias Lopes-PachecoMarcelo M Morales
Nov 3, 2016·BioMed Research International·Guitao LiuHamulati Wufuer
Apr 4, 2017·Respirology : Official Journal of the Asian Pacific Society of Respirology·Jennifer L PerretAlastair Stewart
Apr 10, 2020·Ageing Research Reviews·He-He HuYing-Yong Zhao
Feb 23, 2021·Molecular Therapy. Methods & Clinical Development·Mitchel J R RuigrokWouter L J Hinrichs

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Methods Mentioned

BETA
nuclear translocation
transfection
PCR
Assay
dissection
Protein
ELISA
fluorescence microscopy

Software Mentioned

BLAST
7500
MetaMorph

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