期刊
JOURNAL OF HEPATOLOGY
卷 55, 期 6, 页码 1353-1360出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2011.07.010
关键词
Autophagy; Hepatic stellate cells; Liver fibrosis; LC3B; Bafilomycin A1
资金
- Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
- research council of the Vrije Universiteit Brussel
- Brussels region (ISRIB/''Brustem'')
- IWT
- BELSPO [P6/36]
Background & Aims: Autophagy is a metabolic process that degrades and recycles intracellular organelles and proteins with many connections to human disease and physiology. We studied the role of autophagy during hepatic stellate cell (HSC) activation, a key event in liver fibrogenesis. Methods: Analysis of the autophagic flux during in vitro activation of primary mouse HSCs was performed using a DsRed-GFP-LC3B encoding plasmid. The effect of autophagy inhibition by bafilomycin A1 on the in vitro activation process of human and mouse HSCs was examined by measuring proliferation, presence of activation markers by RT-qPCR, immunofluorescence, and Western blotting. Analysis of lipid droplet and microtubule-associated protein light chain 3 beta (LC3B) colocalization in the presence of PDGF-BB was investigated by immunocytochemistry. Results: A significant increased autophagic flux was observed during culture induced mouse HSC activation. Treatment of mouse HSCs and human HSCs with autophagy inhibitor bafilomycin A1 results in a significant decreased proliferation and expression of activation markers. In addition, lipid droplets and LC3B colocalization was increased after PDGF-BB treatment in quiescent HSCs. Conclusions: During HSC activation, autophagic flux is increased. The demonstration of partly inhibition of in vitro HSC activation after treatment with an autophagy inhibitor unveils a potential new therapeutic strategy for liver fibrosis. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据