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Pathophysiological Analysis of Prion Protein Expression in the Liver

Research Project

Project/Area Number 11670525
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

KAWADA Norifumi  Osaka City University Medical School, Research Associate, 医学部, 助手 (30271191)

Co-Investigator(Kenkyū-buntansha) KANEDA Kenji  Osaka City University Medical School, Professor, 医学部, 教授 (30161186)
池田 一雄  大阪市立大学, 医学部, 助手 (80275247)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordshepatic stellate cels / liver fibrosis / prion protein / 星細胞 / サブトラクション
Research Abstract

We have discovered the prion protein (PrP) gene expression in activated stellate cells by using PCR-select cDNA subtraction method. Northern blot analysis revealed that PrP mRNA was hardly expressed in quiescent stellate cells, but its expression was dramatically augmented in an activated phenotype. Western blot analysis also revealed that PrP expression was enhanced in a time-dependent manner. In in situ hybridization and in imunohistochemistry, PrP and its mRNA expression was detected in liver fibrosis model, in particular along the fibrotic septum accumulating extracellular matrix materials and smooth muscle α-actin-positive cells. In addition, PrP expression was confirmed in human diseased liver tissue with HBV and HCV-induced chronic viral hepatitis and alcoholic liver damage. PrP expression had positive relationship with inflammatory severity. Further analysis indicated that PrP expression was co-localized with the expression of smooth muscle α-actin, indicating that PrP was expressed dominantly in stellate cells. These results indicate that PrP would be utilized as a novel marker for liver fibrosis in the clinical field.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kristensen DB,Kawada N, et al.: "Proteome analysis of rat hepatic stellate cells"Hepatology. 32. 268-277 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitada T,Seki S. et al.: "Clinicopathological characterization of prions a novel marker of human activated stellate"J.Hepatol. 33. 751-757 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang YQ,Ikeda K,Ikebe T, et al.: "Inhibition of hepatic stellate cell proliferation and the semisynthetic analogue of …"Hepatology. 32. 980-989 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimizu S,Yamaelu N,Sawada T,Kawala・N : "In vivo and in vitro interactions between human colon carcinoma cells and …"Jpn.J.Cancer Res. 91. 1285-1295 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okumo M,Akita K,Moriwaki H,Kawada N.: "Prevention of rat hepatic fibrosis by the protease inhibitor cameostert…"Gastroenterology.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horie T, Amagaya S, Kawada N, Hori H, Ito S.: "Effects of sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats"Hepatology. 29. 149-160 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuno M, Sato T, Kitamoto T, Imai S, Kawada N, Suzuki Y, Yoshimura H, Moriwaki H, Onuki K, Masushige S, Muto Y, Friedman SL, Kato S, Kojima S.: "Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis : implication for a potential link between retinoid loss and TGF-b mediated fibrogenesis in vivo."J.Hepatol. 30. 1073-1080 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawada N, Ikeda K, Seki S, Kuroki T.: "Cyclin expression correlates with stellate cell proliferation in culture"J.Hepatol. 30. 1057-1064 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikeda K, Wakahara T, Wang YQ, Kadoya H, Kawada N, Kaneda K.: "In vitro migratory potential of rat quiescent stellate cells and its augmentation by cell activation."Hepatology. 29. 1760-1767 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang LP, Takahara T, Yata Y, Furui K, Jin B, Kawada N, Watanabe A.: "Increased expression of plasminogen activator and plasminogen activator inhibitor during liver fibrogenesis of rats : role of stellate cells."J.Hepatol.. 31. 703-711 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawada N, Seki S, Kuroki T, Kaneda K.: "ROCK inhibitor Y-27632 suppresses stellate cell contraction and portal pressure increase induced by endothelin-1."Biochem.Biophys.Res.Commun.. 266. 296-300 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seki S, Kitada T, Kawada N, Sakaguchi H, Kadoya H, Nakatani K, Satake K, Kuroki T.: "Establishment and characteristics of human hepatocellular carcinoma cells with metastasis to lymph nodes."Hepatogastroenterology. 46. 2812-2817 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kristensen DB, Kawada N, Imamura K, Miyamoto Y, Tateno C, Seki S, Kuroki T, and Yoshizato K.: "Proteome Analysis of Rat Hepatic Stellate Cells."Hepatology. 32. 268-277 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kitada T, Seki S, Ikeda K, Nakatani K, Sakaguchi H, Kawada N, Kadoya H, Kaneda K.: "Clinicopathological characterization of prion : a novel marker of activated human hepatic stellate cells."J.Hepatol.. 33. 751-757 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seki S, Sakaguchi H, Kitada T, Tamori A, Takeda T, Kawada N, Habu D, Nakatani K, Nishiguchi S, Shiomi S.: "Outcomes of dysplastic nodules in human cirrhotic liver : A clinicopathological study."Clin.Cancer Res.. 9. 3469-3473 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang YQ, Ikeda K, Ikebe T, Hirakawa K, Sowa M, Nakatani K, Kawada N, and Kaneda K.: "Inhibition of Hepatic Stellate Cell Proliferation and Activation by the Semisynthetic Analogue of Fumagillin TNP-470 in Rats."Hepatology. 32. 980-989 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimizu S, Yamada N, Sawada T, Ikeda K, Kawada N, Seki S, Kaneda K, Hirakawa K.: "Adult-onset citrullinemia. Pathogenesis of adult-onset type II citrullinemia caused by deficiency of citrin, a mitochindrial solute carrier protein - tissue and subcellular localization of citrin"Jpn.J.Cancer Res.. 91. 1285-1295 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kristeusen DB,Kawadun, et al: "Proteome analysis of rat hepatic stellate cells"Hepatology. 32. 268-277 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitada T.Seki S, et al.: "Clinicopathologyical Characterization of Prion : a novel marker of human activated stellate"J.Hepatol. 33. 751-757 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang YQ,Ikeda K,Ikene T, et al.: "Inhibition of hepatic stellate cell proliferates and the semisynthetic analogue of ・・・"Hepatology. 32. 980-989 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimizu S,YamaeluN Sawades T,LcawalerN: "In vivo and in vitro interaction between human colon carcinoma cells and-"Jpn.J.Cancer Res. 91. 1285-1295 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okumo Li,Alcitak,Uoriwaki H,Kaucele N: "Prevention of rat hepatic fobrosis by the protease inhibitor, Cameostest・・・"Gastroenterology.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawada N, et al.: "ROCK inhibitor Y-27632 Suppresses stellate cell contraction and portalven pressuur induced by endothelin-1"Biochem. Biophys. Res. Commun.. 266. 296-300 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda K, et al.: "In vitro migratory potential of rat quiescent stellate cells and its augmentation by cell activation"Hepatology. 29. 1760-1767 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada N, et al.: "cycclin expression correlate with stellate cell proliferation"J. Hepatology. 30. 1057-1064 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okuno M, et al.: "Increased 9,13-di-cis-retinoic acid in hepatic fibrosis: Inplication for a potential Ink between retinoid loss an TGFβ"J. Hepatology. 30. 1073-1080 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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