Project/Area Number |
25293177
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Osaka City University |
Principal Investigator |
KAWADA NORIFUMI 大阪市立大学, 大学院医学研究科, 教授 (30271191)
|
Co-Investigator(Kenkyū-buntansha) |
Le Thuy 大阪市立大学, 大学院医学研究科, 特任助教 (10572175)
Enomoto Masaru 大阪市立大学, 大学院医学研究科, 准教授 (20423874)
Tamori Akihiro 大阪市立大学, 大学院医学研究科, 准教授 (30291595)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
|
Keywords | 肝がん / サイトグロビン / 肝硬変 / 肝癌 / 線維芽細胞 / 動物モデル |
Outline of Final Research Achievements |
We have shown Cygb's anti-oxidative properties.Here,we clarified the role of Cygb in the development of liver fibrosis and cancer with different aetiologies.Model 1;25ppm DEN treatment for 25 weeks induced liver tumor formation in 100% of Cygb-/- mice compared to 44% in WT mice. Background liver developed fibrosis together with the augmented inflammatory reactions and oxidative stress conditions in Cygb-/- mice. Model 2;8-16 weeks of CDAA treatment provoked more steatohepatitis,fibrosis,and accumulated neutrophils in Cygb-/- mice than in WT.Interestingly,100% of Cygb-/- mice fed CDAA for 32 weeks developed liver cancer,while no tumor was found in WT.HSCs isolated from Cygb-/- mice exhibited the priming condition and the senescence-like phenotype with upregulated chemokine and cytokine mRNA expression and superoxide production.Thus,Cygb deficiency detetiorated liver fibrosis and cancer development caused by different etiologies,indicating the protective role of Cygb in organ insult.
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