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The regulatory mechanisms of osteopontin expression in as a genetic factor to determine inflammatory grading in the liver of HCV infected patients

Research Project

Project/Area Number 19590788
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSaitama Medical University

Principal Investigator

MOCHIDA Satoshi  Saitama Medical University, 医学部, 教授 (20219968)

Co-Investigator(Kenkyū-buntansha) 稲生 実枝  埼玉医科大学, 医学部, 講師 (70286037)
菅原 通子  埼玉医科大学, 医学部, 助教 (20406458)
Co-Investigator(Renkei-kenkyūsha) INAO Mie  埼玉医科大学, 医学部, 講師 (70286037)
SUGAWARA Kayoko  埼玉医科大学, 医学部, 助教 (20406458)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオステオポンチン / 遺伝子多型 / 転写因子 / C 型慢性肝炎 / 性差プロモーターアッセイ / ゲルシフトアッセイ / Th1 系免疫応答 / オシテオポンチン / C型慢性肝炎 / 性差 / プロモーターアッセイ / Th1系免疫応答
Research Abstract

C 型慢性肝炎では男性に比して女性で肝炎活動性が軽微な症例が多いなど,肝病態には性差が認められる。肝炎はTh1 系免疫応答により発症するが,オステオポンチンはその開始に必須のサイトカインであり,肝細胞にその発現が見られる。従って,肝炎活動性は肝細胞の発現するオシテオポンチンによって調節されていると推定され,これが肝病態における性差も規定している可能性がある。我々は,オステオポンチン遺伝子プロモーター領域の塩基配列を解析し,ほぼ100%の連鎖不平衡を呈するnt -155,-616,-1,748 の3SNPs と,これと独立したnt -443 のSNP を見出した。これらSNPs に関して,調節機構を解明するためにPC 解析したところ,nt -443はallele がT の場合にCdxA が,nt -155 は何れのallele でもY 染色体にコードされるSRY が,deletion mutation の場合はoxD3 が結合することが明らかになった。そこで,これらSNPs の結合領域を含む30 塩基からなるoligonucleotide をallele ごとに合成し,ビオチン標識した。一方,雄性のHep 細胞,雌性のHela 細胞にdexamethasone を添加した後に核蛋白質を抽出し,雄性および雌性の活性化核蛋白抽出分画を作成した。標識oligonucleotide と活性化核蛋白抽出分画の混合液を電気泳動してgel-shift アッサイを行ったところ,HepG2 細胞の核抽出物を用いた検討ではCdxA,SRY,FoxD3 と,Hela 細胞での場合にはCdxA,FoxD3 とologonucleotide の結合を示すビオチンシグナルが検出され,オステオポンチンの発現調節に性差があることが確認された。更に,これら一連の検討の過程で,nt -155 の近傍に結合する未知の転写因子が存在することを見出したが,同因子は女性由来の培養細胞には発現しているが,男性由来の細胞には認められないことを発見した。従って,C 型慢性肝疾患における病態の性差は,nt -155 のSNP と男性固有のSRY および女性固有の未知の転写因子によって規定されている可能性があることを明らかにした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (22 results)

All 2009 2008 2007 Other

All Journal Article (16 results) (of which Peer Reviewed: 7 results) Presentation (6 results)

  • [Journal Article] A virulent strain (JIO) of hepatitis E virus genotype 3 emerging and spreading in Japan: analysis of complete or near-complete sequences of eight human and five swine isolates.2009

    • Author(s)
      Takahashi K, Okamoto H, Abe N, Kawakami M, Matsuda H, Mochida S, Sakugawa H, Suginoshita Y, Watanabe S, Yamamoto K, Miyazaki Y, Mishiro S.
    • Journal Title

      Emerg Infect Dis 15

      Pages: 704-709

    • Related Report
      2008 Final Research Report
  • [Journal Article] Donor complications associated with living donor liver transplantation in Japan.2009

    • Author(s)
      Hashikura Y
    • Journal Title

      Transplantation (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A virulent strain (JIO)of hepatitis E virus genotype 3 emerging and Spreading in Japan : analysis of complete or near-complete sequences of eight human and five swine isolates.2009

    • Author(s)
      Takahashi K
    • Journal Title

      Emerg Infect Dis 15

      Pages: 704-709

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intractable Liver Diseases Study Group of Japan. Fulminant hepatitis and late onset hepatic failure in Japan: Summary of 698 patients between 1998 and 2003 analyzed by the annual nationwide survey.2008

    • Author(s)
      Fujiwara K, Mochida S, Matsui A, Nakayama N, Nagoshi S, Toda G
    • Journal Title

      Hepatology Res 38

      Pages: 646-657

    • Related Report
      2008 Final Research Report
  • [Journal Article] Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis.2008

    • Author(s)
      Mochida S, Nakayama N, Matsui A, Nagoshi S, Fujiwara K.
    • Journal Title

      Hepatology Res 38

      Pages: 970-979

    • Related Report
      2008 Final Research Report
  • [Journal Article] Usefulness of anti-ulcer drugs for the prevention and treatment of peptic ulcers induced by low doses of aspirin.2008

    • Author(s)
      Nakashima S, Ota S, Arai S, Yoshino K, Inao M, Ishikawa K, Nakayama N, Imai Y, Nagoshi S, Mochida S.
    • Journal Title

      World J Gastroenterol 15

      Pages: 727-731

    • Related Report
      2008 Final Research Report
  • [Journal Article] Indication criteria for liver transplantation for acute liver failure in Japan.2008

    • Author(s)
      Mochida S.
    • Journal Title

      Hepatol Res 38

      Pages: 852-855

    • NAID

      10025323260

    • Related Report
      2008 Final Research Report
  • [Journal Article] Reevaluation of the Guideline Published by the Acute Liver Failure Study Group of Japan in 1996 to Determine the Indications of Liver Transplantation in Patients with Fulminant Hepatitis2008

    • Author(s)
      Mochida S
    • Journal Title

      Hepatology Research 38

      Pages: 970-979

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fulminant Hepatitis and Late Onset Hepatic Failure in Japan. Summary of 698 Patients between 1998 and 2003 Analyzed by Annual Nationwide Survey2008

    • Author(s)
      Fujiwara K
    • Journal Title

      Hepatology Research 38

      Pages: 646-657

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Full-Length Sequences of Two Hepatitis E Virus Isolates Representing an Eastern China-Indigenous Subgroup of Genotype 4.2007

    • Author(s)
      Koike K, Takahashi K, Mishiro S, Matsui A, Inao M, Nagoshi S, Ohno A, Mochida S, Fujiwara K.
    • Journal Title

      Intervirology 50

      Pages: 181-189

    • Related Report
      2008 Final Research Report
  • [Journal Article] Double Filtration Plasmapheresis and Interferon Combination Therapy for Chronic Hepatitis C Patients with Genotype 1 and High Viral Load.2007

    • Author(s)
      Fujiwara K, Kaneko S, Kakumu S, Sata M, Hige S, Tomita E, Mochida S, The Virus Reduction Therapy Study Group.
    • Journal Title

      Hepatol Res 37

      Pages: 701-710

    • NAID

      10019566447

    • Related Report
      2008 Final Research Report
  • [Journal Article] Influences on Hepatitis B Virus Rplication by a Naturally Occurring Mutation in the Core Gene.2007

    • Author(s)
      Sugiyama M, Tanaka Y, Kurbanov F, Nakayama N, Mochida M, Mizokami M.
    • Journal Title

      Virology 365

      Pages: 285-291

    • Related Report
      2008 Final Research Report
  • [Journal Article] Double filtration plasmapheresis and interferon combination therapy for chronic hepatitis C patients with genotype I and high viral load2007

    • Author(s)
      Mochida S
    • Journal Title

      Hepatology Research 37

      Pages: 701-710

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influences on hepatitis B virus replication by a naturally occurring mutation in the core gene2007

    • Author(s)
      Mochida S
    • Journal Title

      Virology 365

      Pages: 285-291

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Full-length sequences of two hepatitis E virus isolates representing an Eastern China-indigenous subgroup of genotype 42007

    • Author(s)
      Mochida S
    • Journal Title

      Intervirology 50

      Pages: 181-189

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Donor complications associated with living donor liver transplantation in Japan.

    • Author(s)
      Hashikura Y, Ichida T, Umeshita K, Kawasaki S, Mizokami M, Mochida S, Yanaga K, Monden M, Kiyosawa K, The Japanese Liver Transplantation Society.
    • Journal Title

      Transplantation in press

      Pages: 0-0

    • Related Report
      2008 Final Research Report
  • [Presentation] 肝病態の性差を規定する宿主要因: Osteopontin 遺伝子promoter SNPsと新規転写因子の意義2009

    • Author(s)
      濱岡和宏,名越澄子,菅原通子,内木佳代子,稲生実枝,中山伸朗,藤原研司,持田 智
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] 肝病態の性差を規定する宿主要因: Osteopontin 遺伝子promoter SNPs nt -155の意義2008

    • Author(s)
      菅原通子,名越澄子,内木佳代子,濱岡和宏,稲生実枝,中山伸朗,藤原研司,持田 智
    • Organizer
      第8回オステオポンチン研究会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] Hepatic Inflammatory Reaction may be Regulated in Patients with Hepatitis Virus Infection through Osteopontin Expression in Hepatic Macrophages and Hepatocytes Determined by the Genetic Polymorphisms.2007

    • Author(s)
      Sugawara K, Nagoshi S, Hamaoka K, Inao M, Naiki K, Nakayama N, Fujiwara K, MochidaS.
    • Organizer
      Asian Pacific Digestive Diseases Week (APDW) 2007.
    • Place of Presentation
      Kobe, Japan.
    • Related Report
      2008 Final Research Report
  • [Presentation] The Significance of Osteopontin Promoter SNPs at nt -155 and FoxD3 as Host Factors to Regulate the Development of Hepatocellular Carcinoma in Female Patients with HCV Infection.2007

    • Author(s)
      Hamaoka K, Nagoshi S, Sugawara K, Inao M, Naiki K, Naito M, Nakayama M, Fujiwara K, Mochida S.
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston, USA.
    • Related Report
      2008 Final Research Report
  • [Presentation] The Significance of Osteopontin Promoter SNPs at nt-155 and FoxD3 as Host Factors to Regulate the Development of Hepatocellular Carcinoma in Female Patients with HCV Infection2007

    • Author(s)
      Mochida S
    • Organizer
      57th Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Boston,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hepatic Inflammatory Reaction may be Regulated in Patients with Hepatitis Virus Infection through Osteopontin Expression in Hepatic Macrophages and Hepatocytes Determined by the Genetic Polymorphisms2007

    • Author(s)
      Mochida S
    • Organizer
      Asian Pacific Digestive Diseases Week(APDW)2007
    • Place of Presentation
      Kobe,Japan
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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