계명대학교 의학도서관 Repository

Small heterodimer partner attenuates profibrogenic features of hepatitis C virus-infected cells

Metadata Downloads
Author(s)
Gwon-Soo JungJae-Han JeonYeon-Kyung ChoiSe Young JangSoo Young ParkMi-Kyung KimEui-Cheol ShinWon-Il JeongIn-Kyu LeeYu Na KangKeun-Gyu Park
Keimyung Author(s)
Kim, Mi KyungKang, Yu Na
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Journal Title
Liver International
Issued Date
2015
Volume
35
Issue
10
Keyword
AMP-activated protein kinasehepatitis C virusliver fibrosissmall heterodimer partner
Abstract
Background & Aims
An atypical orphan nuclear receptor small heterodimer partner (SHP) is known to be regulated by AMP-activated protein kinase (AMPK). Both of them inhibit TGF-β and Smad signalling and exhibit antifibrotic activity in the liver. However, little is known about the protective effects of SHP and AMPK against hepatitis c virus (HCV)-induced hepatic fibrosis.
Methods
Levels of SHP, p-AMPK and fibrotic markers in HCV-infected human liver and in Huh-7.5 cells infected with HCV genotype 2a (JFH-1) were investigated. The effect of adenovirus-mediated overexpression of SHP (Ad-SHP) and AMPK activation via metformin and 5-amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) on fibrotic gene expression was evaluated in HCV-infected cells. Finally, we examined the effect of Ad-SHP and AMPK activators on invasion and activation of LX2 human HSCs induced by conditioned media from HCV-infected hepatocyte (CM).
Results
In HCV-infected human livers and Huh-7.5 cells infected with HCV, SHP mRNA and protein levels were diminished compared with controls, whereas profibrotic factors were increased. Pharmacological AMPK activation recovered SHP expression, and Ad-SHP inhibited HCV-induced fibrotic gene expression. This finding was accompanied by inhibition of HCV-stimulated nuclear factor-kappa B, an inducer of TGF-β. Moreover, CytoSelect invasion assay revealed that enhanced activity and invasiveness of hepatic stellate cells induced by CM.
Conclusion
These results demonstrate that overexpression of SHP and activation of AMPK reverses profibrogenic features of HCV-infected cells by decreasing TGF-β and fibrotic gene expression. These findings provide a rationale for SHP as a possible therapeutic target against HCV-induced hepatic fibrosis.
Keywords:

AMP-activated protein kinase;
hepatitis C virus;
liver fibrosis;
small heterodimer partner
Keimyung Author(s)(Kor)
김미경
강유나
Publisher
School of Medicine
Citation
Gwon-Soo Jung et al. (2015). Small heterodimer partner attenuates profibrogenic features of hepatitis C virus-infected cells. Liver International, 35(10), 2233–2245. doi: 10.1111/liv.12871
Type
Article
ISSN
1478-3223
Source
http://onlinelibrary.wiley.com/doi/10.1111/liv.12871/epdf
DOI
10.1111/liv.12871
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33398
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.