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Involvement of osteoactivin in inflammatory hepatocarcinogenesis: analysis of mice lacking osteoacitivin expression

Research Project

Project/Area Number 22590742
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKagoshima University

Principal Investigator

IDO Akio  鹿児島大学, 大学院・医歯学総合研究科, 准教授 (30291545)

Research Collaborator OKETANI Makoto  鹿児島大学, 医学部・歯学部附属病院, 講師 (50274816)
UTO Hirofumi  鹿児島大学, 大学院・・医歯学総合研究科, 講師 (20347058)
MORIUCHI Akihiro  鹿児島大学, 医学部・歯学部附属病院, 助教 (40359823)
TAMAI Tsutomu  鹿児島大学, 医学部・歯学部附属病院, 特任講師 (10343336)
KUMAGAI Koutarou  鹿児島大学, 医学部・歯学部付属病院, 特任助教 (80626664)
TABU Kazuaki  鹿児島大学, 医学部・歯学部付属病院, 医員
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsオステオアクチビン / 肝障害 / 肝発癌 / 肝再生 / マクロファージ / 炎症性発癌 / 四塩化炭素 / 自然免疫 / 貪食
Research Abstract

In this study, we investigated an involvement of osteoacitivin, which is expressed in infiltrating macrophages, in repair of injured livers and hepatocarcinogenesis. In mice with CCl4-induced liver injury, osteoactivin was expressed in macrophages infiltrating in injured livers during repair process, and macrophages positive for osteoactivin exhibited enhanced ability of phagocytosis. When macrophages were depleted, repair of injured livers was suppressed. Additionally, mice lacking osteoactivin expression showed inhibition of both fibrosis and its resolution. When hepatoma cells were inoculated, following induction of liver injury, enhanced development of hepatic tumors was observed. These results suggest that osteoactivin play an important role in repair of injured livers and also in development of hepatocellular carcinoma occurring in the context of liver injury.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (20 results)

All 2013 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (9 results)

  • [Journal Article] Intractable Hepato-Biliary Diseases Study Group of Japan. Etiology and prognosis of fulminant hepatitis and late-onset hepatic failure in Japan:Summary of the annual nationwide survey between 2004 and 20092013

    • Author(s)
      Oketani M, Ido A, Nakayama N, Takikawa Y, Naiki T, Yamagishi Y, Ichida T, Mochida S, Onishi S, Tsubouchi H
    • Journal Title

      Hepatol Res

      Volume: 43 Issue: 2 Pages: 97-105

    • DOI

      10.1111/j.1872-034x.2012.01105.x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor stimulates the migration of gastric epithelial cells by altering the subcellular localization of the tight junction protein ZO-12013

    • Author(s)
      Nasu Y, Ido A, Tanoue S, Hashimoto S, Sasaki F, Kanmura S, Setoyama H, Numata M, Funakawa K, Moriuchi A, Fujita H, Sakiyama T, Uto H, Oketani M, Tsubouchi H
    • Journal Title

      J Gastroenterol

      Volume: 48 Issue: 2 Pages: 193-202

    • DOI

      10.1007/s00535-012-0615-y

    • NAID

      10031156305

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy2012

    • Author(s)
      Oketani M, Ido A, Uto H, Tsubouchi H.
    • Journal Title

      Hepatol Res

      Volume: 42 Issue: 7 Pages: 627-636

    • DOI

      10.1111/j.1872-034x.2012.00998.x

    • NAID

      10031144279

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor sustains T regulatory cells and prolongs the survival of kidney allografts in major histocompatibility complex-inbred CLAWN-miniature swine.2012

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

      Transplantation

      Volume: 93 Issue: 2 Pages: 148-155

    • DOI

      10.1097/tp.0b013e31823be83f

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly sensitive lens culinaris agglutinin-reactive alpha-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease2011

    • Author(s)
      Oda K, Ido A, Tamai T, Matsushita M, Kumagai K, Mawatari S, Saishoji A, Kure T, Ohno K, Toyokura E, Imanaka D, Moriuchi A, Uto H, Oketani M, Hashiguchi T, Tsubouchi H
    • Journal Title

      Oncol Rep

      Volume: 26 Pages: 1227-1233

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Repeated enemas with hepatocyte growth factor selectively stimulate epithelial cell proliferation of injured mucosa in rats with experimental colitis2011

    • Author(s)
      Setoyama H, Ido A, Numata M, Moriuchi A, Yamaji N, Tamai T, Funakawa K, Fujita H, Sakiyama T, Uto H, Oketani M, Tsubouchi H
    • Journal Title

      Life Sci

      Volume: 89 Pages: 269-275

    • DOI

      10.3892/or.2011.1294

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety.2011

    • Author(s)
      Ido A, Moriuchi A, Numata M, Murayama T, Teramukai S, Marusawa H, Yamaji N, Setoyama H, Kim ID, Chiba T, Higuchi S, Yokode M, Fukushima M, Shimizu A. and Tsubouchi H.
    • Journal Title

      J. Transl. Med.

      Volume: 9 Issue: 1 Pages: 55-55

    • DOI

      10.1186/1479-5876-9-55

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compaired to dietary fat2011

    • Author(s)
      Shirou Tanoue, Hirofumi Uto, Ryo Kumamoto, et al
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 407 Issue: 1 Pages: 163-168

    • DOI

      10.1016/j.bbrc.2011.02.131

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Changing etiologies and outcomes of acute liver failure: a perspective from Japan2011

    • Author(s)
      Oketani M, Ido A, Tsubouchi H
    • Journal Title

      J Gastroenterology Hepatol

      Volume: 26 Issue: s1 Pages: 65-71

    • DOI

      10.1111/j.1440-1746.2010.06574.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thronbocytopenia exacerbates cholestasis-induced liver fibrosis in mice2010

    • Author(s)
      Kodama T, Takehara T, Hikita H, Shimizu S, Li W, Miyagi T, Hosui A, Tatsumi T, Ishida H, Tadokoro S, Ido A, Tsubouchi H, Hayashi N
    • Journal Title

      Gastroenterology

      Volume: 138 Issue: 7 Pages: 2487-2498

    • DOI

      10.1053/j.gastro.2010.02.054

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma2010

    • Author(s)
      Kanmura S, Uto H, Sato Y, Kumagai K, Sasaki F, Moriuchi A, Oketani M, Ido A, Nagata K, Hayashi K, Stuver SO, Tsubouchi H.
    • Journal Title

      J Gastroenterol

      Volume: 45 Issue: 4 Pages: 459-467

    • DOI

      10.1007/s00535-009-0160-5

    • NAID

      10027215830

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Microenvironment in the repair process of injured livers accelerates development of hepatocellular carcinoma2013

    • Author(s)
      Tabu, K, Ido A, Kumagai K, Oda Kohei, Mawatari S, Tamai T, Moriuchi A, Uto H, Oketani M, Tsubouchi H
    • Organizer
      第19回 Charles Heidelberger 国際がん研究シンポジウム
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Final Research Report
  • [Presentation] Microenvironment in the repair process of injured livers accelerates development of hepatocellular carcinomaliver cancer nodules.2013

    • Author(s)
      Kazuaki Tabu, Akio Ido, Kotaro Kumagai, Kohei Oda, Seiichi Mawatari, Tsutomu Tamai, Akihiro Moriuchi, Hirofumi Uto, Makoto Oketani, and Hirohito Tsubouchi
    • Organizer
      第19回Charles Heidelberger国際がん研究シンポジウム
    • Place of Presentation
      Kagoshima
    • Related Report
      2012 Annual Research Report
  • [Presentation] 障害肝の修復期に浸潤するマクロファージは間葉系細胞の組織再構築に関与する2012

    • Author(s)
      熊谷公太郎, 井戸章雄, 椨 一晃, 大野香織, 小田耕平, 大重彰彦, 今中 大, 馬渡誠一, 玉井 努, 森内昭博, 宇都浩文, 桶谷眞, 坪内博仁
    • Organizer
      第49回日本消化器免疫学会総会
    • Place of Presentation
      鹿児島
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝障害の修復期に浸潤する肝マクロファージの欠損は肝障害を遷延化させる2012

    • Author(s)
      熊谷公太郎, 井戸章雄, 椨 一晃, 大野香織, 小田耕平, 最勝寺晶子, 今中 大, 馬渡誠一, 呉 建, 玉井 努, 森内昭博, 宇都浩文, 桶谷眞, 坪内博仁
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝障害の修復期に浸潤する肝マクロファージの欠損は肝障害を遷延化させる2012

    • Author(s)
      熊谷公太郎、井戸章雄、椨 一晃、大野香織、小田耕平、最勝寺晶子、今中 大、馬渡誠一、呉 建、玉井 努、森内昭博、宇都浩文、桶谷眞、坪内博仁
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 障害肝の修復期に浸潤するマクロファージは間葉系細胞の組織再構築に関与する2012

    • Author(s)
      熊谷公太郎、井戸章雄、椨 一晃、大野香織、小田耕平、大重彰彦、今中 大、馬渡誠一、玉井 努、森内昭博、宇都浩文、桶谷眞、坪内博仁
    • Organizer
      第49回日本消化器免疫学会総会
    • Place of Presentation
      鹿児島市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝炎進展に伴い発現するオステオアクチビンは肝マクロファージの貪食に関与する2011

    • Author(s)
      熊谷公太郎, 井戸章雄, 呉建, 椨一晃, 大野香織, 小田耕平, 最勝寺晶子, 今中大, 馬渡誠一, 玉井努, 森内昭博, 宇都浩文, 桶谷眞, 坪内博仁
    • Organizer
      第15回 JDDW2011
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 障害肝において発現するオステオアクチビンは肝マクロファージの貪食に関与する2011

    • Author(s)
      熊谷公太郎, 井戸章雄, 呉 建, 椨 一晃, 大野香織, 小田耕平, 最勝寺晶子, 今中 大, 馬渡誠一, 玉井 努, 森内昭博, 宇都浩文, 桶谷眞, 坪内博仁
    • Organizer
      第48回日本消化器免疫学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Final Research Report
  • [Presentation] 肝炎の進展過程における炎症の調節因子オステオアクチビンの役割2011

    • Author(s)
      熊谷公太郎, 井戸章雄, 呉建, 高見陽一郎, 佐々木文郷, 小田耕平, 最勝寺晶子, 橋口正史, 馬渡誠一, 玉井努, 森内昭博, 宇都浩文, 桶谷眞, 坪内博仁
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report 2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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