非アルコール性脂肪性肝炎の病態形成におけるサイトグロビンの関与

2014 年度 実施状況報告書

• 研究課題/領域番号: 25860554
• 研究機関: 大阪市立大学
• 研究代表者: LE THUY 大阪市立大学, 医学(系)研究科(研究院), 助教 (10572175)
• 研究期間 (年度): 2013-04-01 – 2016-03-31
• キーワード: 遺伝子

研究実績の概要

In this study, we found that CYGB deficiency promotes liver fibrosis and cancer development in a non-alcoholic steatohepatitis model in mice via activation of oxidative stress pathway (Am J Pathol 2015;185:1045-60). Therefore, the absence of CYGB likely promotes both fibrotic and carcinogenic process in chronic liver disease. CYGB which presences on HSCs and suppresses their activation should be considered primary target for the development of new antifibrotic therapies.

現在までの達成度 (区分)

2: おおむね順調に進展している

理由

Liver fibrosis and cirrhosis accounts for up to 45% of death in developed countries, while we still lack effective antifibrotic therapies.We previously showed that Cygb-deficient mice exhibit susceptibility to cancer development in the liver and lung with diethylnitrosamine administration.Furthermore, in this study, we found that CYGB deficiency promotes liver fibrosis and cancer development in a non-alcoholic steatohepatitis model in mice via activation of oxidative stress pathway.Therefore, the absence of CYGB likely promotes both fibrotic and carcinogenic process in chronic liver disease.The important concern should be the protective role of CYGB in liver fibrosis development. CYGB which presences on HSCs and suppresses their activation should be considered primary target for the development of new antifibrotic therapies.

今後の研究の推進方策

Explore the mechanism action of CYGB in preventing liver fibrosis and cancer development. Recombinant human CYGB protein will be produced and examined its antifibrotic activity. Animal model of alcoholic induced liver diseases will be established.

次年度使用額が生じた理由

謝金の支払いが不要となったため。

次年度使用額の使用計画

物品購入に使用する予定である。

研究成果

• [雑誌論文] Cytoglobin Deficiency Promotes Liver Cancer Development from Hepatosteatosis through Activation of the Oxidative Stress Pathway. (2015)
  • 著者名/発表者名: 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.
  • 雑誌名: Am J Pathol. 巻: 185 ページ: 1045-1060
• [雑誌論文] Involvement of hepatic stellate cell cytoglobin in acute hepatocyte damage through the regulation of CYP2E1-mediated xenobiotic metabolism. (2015)
  • 著者名/発表者名: Teranishi Y, Matsubara T, Krausz KW, Le TT, Gonzalez FJ, Yoshizato K, Ikeda K, Kawada N.
  • 雑誌名: Lab Invest. 巻: 00 ページ: 1-10
  • DOI: 10.1038
• [雑誌論文] (1)Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver. (2014)
  • 著者名/発表者名: 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.
  • 雑誌名: Lab Invest. 巻: 94 ページ: 192-207
  • DOI: 10.1038
• [雑誌論文] 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)
  • 著者名/発表者名: Hai H, Tamori A, Enomoto M, Morikawa H, Uchida-Kobayashi S, Fujii H, Hagihara A, Kawamura E, Thuy le TT, Tanaka Y, Kawada N.
  • 雑誌名: J Gastroenterol Hepatol. 巻: 29 ページ: 201-207
  • DOI: 10.1111
• [学会発表] Cytoglobin Deficiency Promotes Liver Cancer Development from Hepatosteatosis through Activation of the Oxidative Stress Pathway (2014)
  • 著者名/発表者名: Le Thi Thanh Thuy
  • 学会等名: 第28回肝類洞壁細胞研究会学術集会
  • 発表場所: アークホテル岡山(岡山県・岡山市)
  • 年月日: 2014-12-13 – 2014-12-14
• [備考] 大阪市立大学大学院医学研究科 肝胆膵病態内科学ホームページ
  • URL: http://www.med.osaka-cu.ac.jp/liver/index.html