Probucol ameliorates EMT and lung fibrosis through restoration of SIRT3 expression

Publication date: Available online 11 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Hong-Xia Zhang, Yi-Nan Li, Xiu-Li Wang, Chang-Lin Ye, Xiao-Yan Zhu, Hui-Ping Li, Tao Yang, Yu-Jian LiuAbstractPulmonary fibrosis is a progressive fibrotic lung disease with a paucity of therapeutic options. Here we investigated the potential roles of probucol, a cholesterol-lowering drug with potent anti-oxidation properties, on pulmonary epithelial-mesenchymal transition (EMT) and fibrosis. We found that bleomycin-induced lung fibrosis was associated with increased transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA) and decreased E-cadherin expression in lung tissues, indicating EMT formation. Bleomycin treatment resulted in an induction of oxidative stress in lung tissues. Probucol treatment attenuated bleomycin-induced TGF-β1 production, EMT and pulmonary fibrosis, meanwhile it suppressed bleomycin-induced oxidative stress. Bleomycin treatment resulted in decreases in protein expressions of Sirtuin 3 (SIRT3) in the lung, which were restored by ROS scavenger NAC and probucol treatment, suggesting that probucol might restore SIRT3 expression by suppressing bleomycin-induced oxidative stress. In the mouse alveolar type II epithelial cell line MLE-12, probucol treatment leads to an increase in SIRT3 expression in bleomycin-treated AT-II cells, which might contribute to the inhibitory effect of probucol on EMT through suppressing hypoxia inducible factor (HIF...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research