Probucol ameliorates EMT and lung fibrosis through restoration of SIRT3 expression.
Authors of this article are:
Zhang HX, Li YN, Wang XL, Ye CL, Zhu XY, Li HP, Yang T, Liu YJ.
A summary of the article is shown below:
Pulmonary 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)-1α/TGF-β1 pathway. In addition, probucol inhibited bleomycin-induced macrophage infiltration in the lung. Bleomycin decreased SIRT3 protein expression, whereas increased HIF-1α activation and TGF-β1 release in the mouse macrophage cell line RAW264.7, which were attenuated by probucol treatment. Taken together, the present study suggests that probucol may ameliorate EMT and lung fibrosis through restoration of SIRT3 expression. The data obtained in this study provides proof for the idea that probucol may be a potential therapeutic option for the treatment of pulmonary fibrosis.Copyright © 2019. Published by Elsevier Ltd.
Check out the article’s website on Pubmed for more information:
This article is a good source of information and a good way to become familiar with topics such as: Epithelial-mesenchymal transition; Lung fibrosis; Oxidative stress; Probucol; SIRT3.