title: The anti-hepatic fibrosis activity of ergosterol depended on upregulation of PPARgamma in HSC-T6 cells.
abstract: Advanced glycation endproducts (AGEs) were shown to play an important role in metabolic syndrome and were suggested to contribute to the development of hepatic fibrosis. Evidence indicates that AGEs resulted in hepatic fibrosis coupled to the activation of the receptor for AGEs (RAGE) in hepatic stellate cells (HSCs). NADPH oxidase is downstream of the RAGE signaling pathway, resulting in an increase in reactive oxygen species (ROS), alpha-smooth muscle actin (alpha-SMA), RAGE, and matrix metalloproteinase-9 (MMP-9). This study was designed to evaluate the effects of ergosterol on RAGE signaling in HSC-T6 cells. Ergosterol suppressed the activation of HSC-T6 cells induced by AGEs, and attenuated overexpressions of alpha-SMA, MMP-9, and epithelial-mesenchymal transition (EMT) markers, including N-cadherin and vimentin. We also found that these inhibitory effects of ergosterol on the activation of HSCs were dependent on peroxisome proliferator-activated receptor-gamma (PPARgamma) confirmed by PPARgamma reporter assay and PPARgamma knockdown. In addition, ergosterol also showed an inhibitory effect on the generation of AGEs, fructosamine, and α-dicarbonyl compounds in this study. Our results show that ergosterol can be used as a protective agent against hepatic fibrosis caused by induction of AGEs.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan and Department of Chinese Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan.
authors.forename: Chen-Jei
authors.initials: CJ
authors.lastname: Tai
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chen-Yen
authors.initials: CY
authors.lastname: Choong
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University Hospital, Taipei, Taipei 11031, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medicine University Hospital, Taipei 11031, Taiwan. cjtai@tmu.edu.tw ycshi@healthtib.com and Taiwan Indigena Botanica Co., Ltd, Taipei City 11494, Taiwan.
authors.forename: Yeu-Ching
authors.initials: YC
authors.lastname: Shi
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medicine University Hospital, Taipei 11031, Taiwan. cjtai@tmu.edu.tw ycshi@healthtib.com and Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Cheng-Jeng
authors.initials: CJ
authors.lastname: Tai
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004875:Ergosterol / Q000008:administration & dosage*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015820:Cadherins; D017127:Glycation End Products, Advanced; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D020780:Matrix Metalloproteinase 9; D004875:Ergosterol