Clin Mol Hepatol > Accepted Articles
Auranofin attenuates hepatic steatosis and fibrosis in non-alcoholic fatty liver disease via NRF2 and NF-κB signaling pathways
Seung Min Lee1, Dong Hee Koh2, Dae Won Jun1,3, Yoon Jin Roh4, Hyeon Tae Kang5, Ju Hee Oh1, Hyun Sung Kim6
1Department of Translational Medicine, Graduate School of Biomedical Science & Engineering, Hanyang University, Seoul, Republic of Korea
2Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital
3Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
4Department of Dermatology, Chung-Ang University Hospital, Seoul, South Korea
5Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul, Korea
6Department of pathology, Hanyang University College of Medicine, Seoul, Republic of Korea
Correspondence :  Dae Won Jun ,
Tel: +82-2-2290-8338, Fax: +82-2-972-0068, Email: noshin@hanyang.ac.kr
Yoon Jin Roh ,
Tel: +82-2-6299-3088, Email: shdbswls@cau.ac.kr
Received: March 10, 2022  Revised: June 7, 2022   Accepted: June 18, 2022
ABSTRACT
Background & Aim
We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro.
Material & Methods
Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the GSEA analysis program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with TGFβ1 and PA, respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated.
Results
Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including THBS1, ET-1, FN-1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the ROS pathway and decreased in the inflammatory response. Auranofin decreased NF-κB and IκBα in TGFβ1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation (BDL) model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a western diet (WD).
Discussion
Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.
KeyWords: non-alcoholic fatty liver disease, hepatic fibrosis, auranofin, antioxidant, lipid accumulation

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