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The differentiating regulation from bone marrow stem cells and hepatic stem cells to hepatocytes and bile-duct cells as a tool of treatment against hepatic failure

Research Project

Project/Area Number 17390103
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKobe University

Principal Investigator

HAYASHI Yoshitake  Kobe University, School of Medicine, Professor (50189669)

Co-Investigator(Kenkyū-buntansha) KU Yonson  Kobe University, School of Medicine, Professor (40195615)
SEO Yasushi  Kobe University, School of Medicine, Assistant Professor (90362772)
KANOMATA Naoki  Kawasaki Medical University, Lecturer (60263373)
MASIWA Yoshimasa  Kobe University, Graduate School of Medicine, Assistant Professor (50362778)
TSUJIMURA Tohru  Hyogo College of Medicine, 医学部, Professor (20227408)
矢野 嘉彦  神戸大学, 医学部附属病院, 学術推進研究員 (60419489)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥15,080,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsSgIGSF / Oval cell / FoxO1 / Hepatocyte / Regenerative medicine / PI3-kinase / Akt / Diabetes Mellitus / Insulin resistance / 人体病理 / 肝臓 / FoxO1 / HBV / HCV / 遺伝子多型 / 骨髄幹細胞 / oval cell / NASH
Research Abstract

In fluminant hepatitis or Small Size for Graft cases, it is the most important that rapid recovery from liver failure is induced. Forkhead transcription factor FoxO mediates the function and differentiation of hepatocytes. And transfer from nuclear (active as a transcriptional nuclear protein) to cytoplasm (inactive) is controlled by PI3-kinase/Akt depending phosphorysation cascade. The new binding protein to FoxO1, P13, which is essential for adipocyte-differentiation and play an important role as a repressor of FoxO1, a transcriptional regulator and sensitizer of insulin, was found out. (J Clin Investigation 116(9): 2473-83, 2006; Diabetes in press; the 19^th Molecular Diabetology Symposium, Kobe).
SgIGSF is an intercellular adhesion molecule of the nectin-like family. In developing mouse liver, SgIGSF expression was transiently upregulated at perinatal ages and was restricted to the lateral membrane of biliary epithelial cells (BECs). To investigate the role of SgIGSF in bile duct/ductule formation, An in vitro model, in which rat hepatocyte aggregates embedded in collagen gels containing insulin and epidermal growth factor extend epithelial sheets and processes in the first week and form ductules within a month, was used. The process and ductular cells were continuously positive for SgIGSF and cytokeratin 19, a BEC marker. When the aggregate culture was started in the presence of a function-blocking anti-SgIGSF antibody, the number of epithelial processes per aggregate was reduced by 80%. These data suggests that SgIGSF is a novel and functional BEC adhesion molecule that is expressed for a limited time during active bile duct/ductule formation. (Hepatology, 45:684-694, 2007)

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (56 results)

All 2007 2006 2005 Other

All Journal Article (50 results) (of which Peer Reviewed: 23 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] SgIGSF is a novel biliary-epithelial-cell adhesion molecule mediating duct/ductule development2007

    • Author(s)
      Ito A
    • Journal Title

      Hepatol 45

      Pages: 684-694

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Cycloxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophagcal cancer recurrence2007

    • Author(s)
      Yoshikawa R
    • Journal Title

      World J Gastroenterol 13

      Pages: 2283-2288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oncostatin M Gene Therapy Attenuates Liver Damage Induced by Dimethylnitros aminc in Rats2007

    • Author(s)
      Hamada T
    • Journal Title

      Am J Pathol 171

      Pages: 872-881

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • 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(Suppl1)

      Pages: 58-66

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • 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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • 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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • 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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Variations in the core promoter/pre-core region in HBV genotype C in Janapanese and Northern Vietnamese patients2007

    • Author(s)
      Truong BX
    • Journal Title

      J Med Virol 79

      Pages: 229-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • 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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency2007

    • Author(s)
      Takahashi Y
    • Journal Title

      Gastroenterology 132(3)

      Pages: 938-943

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] SgIGSF is a novel biliary-epithelial-cell adhesion molecule mediating duct/ductule development2007

    • Author(s)
      Ito, A, et. al.
    • Journal Title

      Hepatology 45

      Pages: 684-694

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cycloxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence2007

    • Author(s)
      Yoshikawa, R, et. al.
    • Journal Title

      World J Gastroenterol 13

      Pages: 2283-2288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Superiority of CT arterioport al a ngiography to contrast-enhanced CT and MRI in the diagnosis of hepatocellular carcinoma in nodules smaller than 2 cm2007

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

      Oncology, 72 Suppl 1

      Pages: 58-66

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Well-to moderately-differentiated HCC manifesting hyperattenuation on both CT during arteriography and arterial portography2007

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

      World J Gastroenterol 13

      Pages: 5775-5778

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Double-layered collagen gel hemisphere for cell invasion assay: successful visualization and quantification of cell invasion activity2007

    • Author(s)
      Takata, Mm, et. al.
    • Journal Title

      Cell Commun Adhes 14

      Pages: 157-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] apanese case of hepatitis B virus genotypes C/D hybrid2007

    • Author(s)
      Yano, Y, et. al.
    • Journal Title

      Hepatol Res 37

      Pages: 1095-1099

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients2007

    • Author(s)
      Truong, BS, et. al.
    • Journal Title

      J Med Virol 79

      Pages: 229-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Small hepatocellular carcinoma presenting with massive metastasis in the peritoneum, mimicking sarcomatous tumor2007

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

      Hepatol Res 37

      Pages: 885-889

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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, et. al.
    • Journal Title

      World J Gastroenterol 13

      Pages: 1271-1274

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Growth hormone reverses nonalcoholic sten tohepatitis in a patient with adult growth hormone deficiency2007

    • Author(s)
      Takahashi, Y, et. al.
    • Journal Title

      Gastroenterology 132(3)

      Pages: 938-943

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] SgIGSF is novel biliary-epithelial-cell adhesion molecule mediating duct/ductile development2007

    • Author(s)
      Ito A
    • Journal Title

      Hepatol 45

      Pages: 684-694

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cycloxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence2007

    • Author(s)
      Yoshikawa R
    • Journal Title

      World J Dastroenterol 13

      Pages: 2283-2288

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncostatin M Gene Therapy Attenuates Liver Damage Induced by Dimethylnitros amine in Rats2007

    • Author(s)
      Hamada T
    • Journal Title

      Am J Pathol 171

      Pages: 872-881

    • 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 amaller 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] 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] 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: 229-235

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development2007

    • Author(s)
      Ito A
    • Journal Title

      Hepatology 45・3

      Pages: 684-694

    • Related Report
      2006 Annual Research Report
  • [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] The LXXLL motif of murine forkhead transcription factor FoxOl mediates Sirtl-dependent transcriptional activity2006

    • Author(s)
      Nakae J
    • Journal Title

      J Clin Investigation 116(9)

      Pages: 2473-2483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The LXXLL motif of murine forkhead transcription factor PoxO1 mediates Sirtl-dependent transcriptional activity2006

    • Author(s)
      Nakae, J, et. al.
    • Journal Title

      J Clinical Investigation 116(9)

      Pages: 2473-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
  • [Journal Article] Placement of Self-expanding Stents with Different Diameters in the Porcine Venous System : An Experimental Study2006

    • Author(s)
      Yamaguchi M
    • Journal Title

      J Vasc Interv Radiol. 17・1

      Pages: 113-119

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Well differentiated HCC manifesting hyper attenuation on CT during arterial portography2005

    • Author(s)
      Kim SR
    • Journal Title

      Hepato-Gasteroenterology 52・65

      Pages: 1559-1562

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-alpha2005

    • Author(s)
      Truong BX
    • Journal Title

      Int J Mol Med 16・2

      Pages: 279-284

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interferon-beta induction/interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C2005

    • Author(s)
      Kim KI
    • Journal Title

      Int J Clin Pharmacol Res 25・2

      Pages: 71-76

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Serum hepatitis B virus DNA levels differentiating inactive carriers from patients with chronic hepatitis B2005

    • Author(s)
      Seo Y
    • Journal Title

      Eur J Gasteroenterol Hepatol 17・7

      Pages: 753-757

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Primary sclerosing cholangitis and hepatitis C virus infection2005

    • Author(s)
      Kim SR
    • Journal Title

      Intervirology 48・4

      Pages: 268-272

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

    • Author(s)
      Miki A
    • Journal Title

      International Journal of Oncology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation

    • Author(s)
      Syampurnawat M
    • Journal Title

      Leuk Res. 2008 Jan 2;[Epub ahead of print]

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Forkhead transcription factor FoxO1 in adipose tissues regulates energy storage and expenditure

    • Author(s)
      Nakae J
    • Journal Title

      Diabetes. 2007 Dec 27; [Epub ahead of print]

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oncostatin M Gene Therapy Attenuates Liver Damage Induced by Dimethylnitrosatnine in Rats

    • Author(s)
      Hamada, T, et. al.
    • Journal Title

      km J Palhol 171

      Pages: 872-881

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

    • Author(s)
      Miki, A, et. al.
    • Journal Title

      Intl J of Oncol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation

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

      Leuk Res 1 (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Forkhead transcription factor FoxO1 in adipose tissues regulates energy storage and expenditure

    • Author(s)
      Nakae, J, et. al.
    • Journal Title

      Diabetes (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model

    • Author(s)
      Miki A
    • Journal Title

      International Journal of Oncology (in press)

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

    • Author(s)
      Syampurnawat M
    • Journal Title

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

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

    • Author(s)
      Nakae J
    • Journal Title

      Diabetes. 2007 Dec 27 (Epub ahead of print)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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シウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-12-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] New binding protein to Fox01, which is important for gluco-metabolism2007

    • Author(s)
      Nakae, J, et. al.
    • Organizer
      the 19th Molecular Diabetology Symposium
    • Place of Presentation
      Kobe
    • Year and Date
      2007-12-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Pathological analysis of NASH (nonalcoholic steatohepatitis) model mouse established by Endothelial lipase gene destruction2007

    • Author(s)
      Miki, A, et. al.
    • Organizer
      DDW-Japan 2007
    • Place of Presentation
      Kobe
    • Year and Date
      2007-10-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

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

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

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

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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