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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| Project Status |
Completed (Fiscal Year 2015)
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| 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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| Keywords | 遺伝子 / サイトグロビン / ｻｲﾄｸﾞﾛﾋﾞﾝ / CYGB / HSCS / NASH / LIVER FIBROSIS / LIVER CANCER / OXIDATIVE STRESS |
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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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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Cytoglobin Deficiency Promotes Liver Cancer Development from Hepatosteatosis through Activation of the Oxidative Stress Pathway.2015
Author(s)
Thuy le TT,Matsumoto Y,Thuy Tuong TV, Hai H,Suoh M,Urahara Y,Motoyama H,Fujii H,Tamori A,Kubo S,Takemura S,Morita T,Yoshizato K, and Kawada N.
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Journal Title
Am J Pathol.
Volume: 185
Pages: 1045-1060
Related Report
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[Journal Article] (1)Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.2014
Author(s)
Motoyama H, Komiya T, Thuy le TT, Tamori A, Enomoto M, Morikawa H, Iwai S, Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Murakami Y, Yoshizato K, Kawada N.
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Journal Title
Lab Invest.
Volume: 94
Pages: 192-207
Related Report
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[Journal Article] Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin.2014
Author(s)
Hai H, Tamori A, Enomoto M, Morikawa H, Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Thuy le TT, Tanaka Y, Kawada N.
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Journal Title
J Gastroenterol Hepatol.
Volume: 29
Pages: 201-207
Related Report
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[Journal Article] Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver2014
Author(s)
Hiroyuki Motoyama, Tohru Komiya, Le Thi Thanh Thuy, Akihiro Tamori, Masaru Enomoto, Hiroyasu Morikawa, Shuji Iwai, Sawako Uchida-Kobayashi, Hideki Fujii, Atsushi Hagihara, Etsushi Kawamura, Yoshiki Murakami, Katsutoshi Yoshizato, and Norifumi Kawada
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Journal Title
Laboratory Investigation
Volume: 94
Issue: 2
Pages: 194-207
DOI
Related Report
Peer Reviewed
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