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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kagoshima 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
• 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

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.

Research Products

• [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 2009 (2013)
  • 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 Pages: 97-105
  • DOI: DOI:10.1111/j.1872-034X.2012.01105.x
  • 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-1 (2013)
  • 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 Pages: 193-202
  • DOI: DOI:10.1007/s00535-012-0615-y
  • Peer Reviewed
• [Journal Article] Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy (2012)
  • Author(s): Oketani M, Ido A, Uto H, Tsubouchi H.
  • Journal Title: Hepatol Res Volume: 42 Pages: 627-636
  • DOI: DOI:10.1111/j.1872-034X.2012.00998.x
  • 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 disease (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Repeated enemas with hepatocyte growth factor selectively stimulate epithelial cell proliferation of injured mucosa in rats with experimental colitis (2011)
  • 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: DOI:10.3892/or.2011.1294
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor ameliorates mucosal injuries, leading to inhibition of colon cancer development in mice (2011)
  • Author(s): Yamaji N, Ido A, Moriuchi A, Numata M, Setoyama H, Tamai T, Funakawa K, Fujita H, Sakiyama T, Uto H, Oketani M, Tsubouchi H
  • Journal Title: Oncol Rep Volume: 26 Pages: 335-341
  • DOI: DOI:10.3892/or.2011.1294
  • Peer Reviewed
• [Journal Article] Safety and 8. pharmacokinetics of recombinant human hepatocyte growth factor 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, Tsubouchi H
  • Journal Title: J Transl Med Volume: 55
  • DOI: DOI:10.1186/1479-5876-9-55
  • Peer Reviewed
• [Journal Article] Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compared to dietary fat (2011)
  • Author(s): Tanoue S, Uto H, Kumamoto R, Arima S, Hashimoto S, Nasu Y, Takami Y, Moriuchi A, Sakiyama T, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 163-168
  • DOI: DOI:10.1016/j.bbrc.2011.02.131
  • Peer Reviewed
• [Journal Article] Changing etiologies and outcomes of acute liver failure: a perspective from Japan (2011)
  • Author(s): Oketani M, Ido A, Tsubouchi H
  • Journal Title: J Gastroenterology Hepatol Volume: 26 Pages: 65-71
  • DOI: DOI:10.1111/j.1440-1746.2010.06574.x
  • Peer Reviewed
• [Journal Article] Thronbocytopenia exacerbates cholestasis-induced liver fibrosis in mice (2010)
  • 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 Pages: 2487-2498
  • DOI: DOI:10.1053/j.gastro.2010.02.054
  • Peer Reviewed
• [Journal Article] The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma (2010)
  • 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 Pages: 459-467
  • DOI: DOI:10.1007/s00535-009-0160-5
  • Peer Reviewed
• [Presentation] Microenvironment in the repair process of injured livers accelerates development of hepatocellular carcinoma (2013)
  • 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
  • Year and Date: 20130200
• [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
  • Year and Date: 20120700
• [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
  • Year and Date: 20120600
• [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
  • Year and Date: 20111000
• [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
  • Year and Date: 20110700
• [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
  • Year and Date: 20110600