2015 Fiscal Year Final Research Report
Loss of Cytoglobin Exacerbates Liver Fibrosis and Cancer Development in Steatohepatitis by Activating the Oxidative Stress Pathaway
| Project/Area Number |
25860554
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka City University |
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Principal Investigator |
LE THUY 大阪市立大学, 大学院医学研究科, 特任助教 (10572175)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 遺伝子 / サイトグロビン |
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| Outline of Final Research Achievements |
Cytoglobin was discovered in 2001 as a protein expressed uniquely in hepatic stellate cell.The present study clarifies the role of Cygb in steatohepatitis induced by a choline-deficient amino acid-defined dietin mice.CDAA treatment for 8 weeks induced prominent inflammation and fibrosis in Cygb-/- mice,which was inhibited by macrophage deletion.Suprisingly,at 32 weeks,despite no tumor formation in the WT mice,all Cygb-/- mice developed liver cancer,which was ameliorated by N-acetylcysteine treatment.Altered expression of 31 genes involved in the metabolism of reactive oxygen species was notable in Cygb-/- mice.Moreover,primary untreated-HSCs isolated from Cygb-/- mice showed a pre-activated condition characterised by augmented ROS and cytokine production.In human NASH livers,the expression of CYGB was declined in a negative correlation with increased NASH acore.A similar decline in CYGB protein and mRNA expression likely contributes to the development of human NASH and liver cancer.
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| Free Research Field |
肝臓病学
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