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肝炎ウイルス非感染肝細胞癌発生の分子機序の解明

Research Project

Project/Area Number 18659097
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionKobe University

Principal Investigator

林 祥剛  Kobe University, 医学部, 教授 (50189669)

Co-Investigator(Kenkyū-buntansha) 福本 巧  神戸大学, 医学部, 准教授 (70379402)
鹿股 直樹  川崎医科大学, 講師 (60263373)
矢野 嘉彦  神戸大学, 医学部附属病院, 特定助教 (60419489)
眞庭 謙昌  神戸大学, 大学院・医学系研究科, 助教 (50362778)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsNASH / 脂肪性肝炎 / Endothelial lipase / アディポネクチン / 非ウイルス性肝炎 / 非ウイルス性肝癌 / 酸化ストレス / インスリン抵抗性 / 非B非C肝炎 / cryptogenic cirrhosis / Fox01 / インターフェロン / pegylated interferon / Nonalcoholic steatohepatitis(NASH) / メタボリック症候群 / 脂肪肝 / アルコール性肝炎 / adipocytokine / 血管内皮リパーゼ
Research Abstract

近年、脂肪肝から肝硬変および肝癌への進展が問題視されています。脂質代謝に関連のある血管内皮リパーゼ(Endothelial lipase; EL)をKnock outしたマウスに高脂肪食を与えると、単なる脂肪肝ではなくNASHが発生することを見出し、このマウスの病態を解明することによりヒトにおけるNASHの病態解明の一助になると考える。このマウスにおける脂肪性肝炎の発生機序としてELが欠如しているため脂肪細胞での脂肪分解が低下し脂肪細胞の肥大化と脂肪細胞から分泌されるアディポサイトカインの分泌異常が起こりインスリン抵抗性を惹起したと考えられた。それに伴い高インスリン血症が誘導され、肝臓での脂肪酸の流入増加と酸化ストレスの上昇から脂肪性肝炎を引き起こした可能性が考えられた。脂肪性肝炎の発症機序としてすでに2ヒットセオリーが提唱されている、これは1st Fitとして脂肪肝やそれに伴うインスリン抵抗性のある状態に2nd Fitとして酸化ストレスや脂質過酸化、炎症性サイトカインが加わり脂肪性肝炎を発症するとされるものである。このモデルにおいても普通食のKOマウスにおいては脂肪性肝炎は認めず高脂肪食負荷のKOマウスに脂肪性肝炎を認めたことから1st fit 2^<nd> fit両者の存在で脂肪性肝炎を発症することが証明された。結論Endothelial lipase KO mouseにおけるNASH発生機序としてインスリン抵抗性、炎症性サイトカインの増加、アディポネクチンの低下が関与している可能性が示唆された。
(the 18th Confbrence of the Asian Pacific Association fbr the Study of the Liver,ソウル、韓国)

Report

(3 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 13 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma.2008

    • Author(s)
      Taniguchi M, et al.
    • Journal Title

      World J Gastroenterol. 14(13)

      Pages: 1997-2002

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Usefulness of a new immunoradiometric assay of HCV core antigen to predict virological response during PEG-IFN/RBV combination therapy for chronic hepatitis with high viral load of serum HCV RNA genotype 1b.2008

    • Author(s)
      Sasase N, et al.
    • Journal Title

      Intervirology. 51 Suppl 1

      Pages: 70-75

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Focal nodular hyperplasia-like lesion with venous washout in alcoholic liver cirrhosis.2008

    • Author(s)
      Kim SR, et al.
    • Journal Title

      Intern Med 47(21)

      Pages: 1899-1903

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model2008

    • Author(s)
      Miki A
    • Journal Title

      International Journal of Oncology 32(In press)

      Pages: 603-608

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation2008

    • Author(s)
      Syampurnawat M
    • Journal Title

      Leuk Res. 2008 Jan 2 32(Epub ahead of print)

      Pages: 1141-1143

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Forkhead transcription factor FoxO1 in adipose tissues regulates energy storage and expenditure2008

    • Author(s)
      Nakae J
    • Journal Title

      Diabetes. 2007 Dec 27 57(Epub ahead of print)

      Pages: 563-576

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Superiority of CT arterioportal angiography to contrast-enhanced CT and MRI in the diagnosis of hepatocellular carcinoma in nodules smaller than 2 cm2007

    • Author(s)
      Kim SR
    • Journal Title

      Oncology 72(Suppl 1)

      Pages: 58-66

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Well-to moderately-differentiated HCC manifesting hyperattenuation on both CT during arteriography and arterial portography2007

    • Author(s)
      Kim SR
    • Journal Title

      World J Gastroenterol 13

      Pages: 5775-5778

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Double-layered collagen gel hemisphere for cell invasion assay: successful visualization and quantification of cell invasion activity2007

    • Author(s)
      Takata M
    • Journal Title

      Cell Commun Adhes 14

      Pages: 157-167

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Japanese case of hepatitis B virus genotypes C/D hybrid2007

    • Author(s)
      Yano Y
    • Journal Title

      Hepatol Res 37

      Pages: 1095-1099

    • NAID

      10019796558

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients2007

    • Author(s)
      Truong BX
    • Journal Title

      J Med Virol 79

      Pages: 1293-1304

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small hepatocellular carcinoma presenting with massive metastasis in the peritoneum, mimicking sarcomatous tumor2007

    • Author(s)
      Kim SR
    • Journal Title

      Hepatol Res 37

      Pages: 885-889

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis2007

    • Author(s)
      Kim SR
    • Journal Title

      World J Gastroenterol 13

      Pages: 1271-1274

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular epidemiological study of hepatitis B virus infection in two different ethnic populations from the Solomon Islands2007

    • Author(s)
      Utsumi T
    • Journal Title

      J Med Virol. 79・3

      Pages: 229-235

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam2007

    • Author(s)
      Truong BX
    • Journal Title

      Int J Mol Med 19・2

      Pages: 293-299

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.2006

    • Author(s)
      Kim SR
    • Journal Title

      World J Gastroenterol 12・41

      Pages: 6727-6729

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity2006

    • Author(s)
      Nakae J
    • Journal Title

      J Clin Invest. 116・9

      Pages: 2473-2483

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and acquiring HBsAb after IFN and lamivudine treatment2006

    • Author(s)
      Kim SR
    • Journal Title

      Hepatol Res 36・2

      Pages: 149-152

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genome-wide microsatellite analysis of focal nodular hyperplasia : a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma2006

    • Author(s)
      Nakayama s
    • Journal Title

      J Hepatobiliary Pancreat Surg 13・5

      Pages: 416-420

    • Related Report
      2006 Annual Research Report
  • [Presentation] 新規FoxO1結合蛋白による糖代謝調節2007

    • Author(s)
      中江 淳
    • Organizer
      第19回分子糖尿病学シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-12-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] Endothelial lipase knock outマウスにおけるNASH(非アルコール性脂肪性肝炎)の病態解析2007

    • Author(s)
      三木 章
    • Organizer
      第11回日本肝臓学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2007-10-19
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kobe-u.ac.jp/molgene/index-jp.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kobe-u.ac.jp/molgene/index-jp.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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