Journal article
Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
The Journal of clinical investigation, Vol.112(7), pp.989-998
10/01/2003
DOI: 10.1172/JCI200317970
PMCID: PMC198521
PMID: 14523036
Abstract
Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration. In order to investigate the hepatoprotective effects of Stat3, we examined whether Stat3 protects against Fas-mediated liver injury in the mouse. A constitutively activated form of Stat3 (Stat3-C) was adenovirally overexpressed in mouse liver by intravenous injection, and then a nonlethal dose of Fas agonist (Jo2) was injected intraperitoneally into the mouse (0.3 μg/g body wt). Stat3-C dramatically suppressed both apoptosis and necrosis induced by Jo2. In contrast, liver-specific Stat3-knockout mice failed to survive following Jo2 injection. Stat3-C upregulated expression of FLICE inhibitor protein (FLIP), Bcl-
X
L, and Bcl-2, and accordingly downregulated activities of FLICE and caspase-3 that were redox-independent. Interestingly, Stat3-C also upregulated the redox-associated protein redox factor-1 (Ref-1) and reduced apoptosis in liver following Jo2 injection by suppressing oxidative stress and redox-sensitive caspase-3 activity. These findings indicate that Stat3 activation protects against Fas-mediated liver injury by inhibiting caspase activities in redox-dependent and -independent mechanisms.
Details
- Title: Subtitle
- Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
- Creators
- Sanae Haga - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAKeita Terui - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAHui Qi Zhang - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAShin Enosawa - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAWataru Ogawa - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAHiroshi Inoue - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USATorayuki Okuyama - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAKiyoshi Takeda - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAShizuo Akira - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USATetsuya Ogino - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAKaikobad Irani - Johns Hopkins University School of MedicineMichitaka Ozaki - Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Division of Diabetes and Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.112(7), pp.989-998
- DOI
- 10.1172/JCI200317970
- PMID
- 14523036
- PMCID
- PMC198521
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 10/01/2003
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984312977502771
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