| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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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