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Investigation of molecular mechanism in the development of chronic obstructive pulmonary disease (COPD) using transgenic animal models.

Research Project

Project/Area Number 14570538
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionGunma University

Principal Investigator

SUGA Tatsuo  Gunma University, Second Department of Internal Medicine, Assistant Professor, 医学部, 助手 (50334115)

Co-Investigator(Kenkyū-buntansha) NAGAI Ryozo  The University of Tokyo Hospital, Department of Cardiovascular Medicine, Professor, 医学部附属病院, 教授 (60207975)
KURABAYASHI Masahiko  Gunma University, Second Department of Internal Medicine, Professor, 医学部, 教授 (00215047)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsChronic obstructive pulmonary disease (COPD) / Animal model of COPD / klotho mutant mouse / Molecular biology
Research Abstract

1.Analysis of the pulmonary emphysema in homozygous mutant klotho mouse (KL-/-).
(1)Comparison of the gene-expression profile in the lung between KL-/-and wild-type mouse (WT).
KL-/-, which lacks the klotho gene expression, develops emphysema at 4 weeks of age. We compared the gene-expression profile in the lung between KL-/-and WT at 2 weeks of age through hybridization method using Atlas Nylon Membranes. The genes including caspase 3, radical fringe homolog precursor related to a Notch signal transduction pathway, activin receptor IIA, IIB, and MAD homolog 7 related to TGF-beta family protein, were expressed more intensively in KL-/-lung than in WT lung. On the other hand, serine protease inhibitor 2 gene expressed less intensively in KL-/-lung. These findings suggest that deranged expression of the genes associated with lung development and apoptosis of pulmonary constituting cells participates in the pathogenesis of emphysema in klotho mice. The suppression of protease inhibitor activity, which protects lung from various injuries, is another contributing factor of it.
(2)Investigation of therapy for emphysema In KL-/-.
In male KL-/-, dietary phosphorus restriction upregulates the klotho gene expression. We investigated whether the upregulation of the klotho gene ameliorates emphysema in KL-/-. KL-/-at 3 weeks (younger group) and 5 weeks (elder group) were fed with phosphorus restricted (0.4%-P) diet for 2 and 4 weeks, respectively. The lungs of younger group did not develop emphysema while those of elder group showed severe emphysema. The replenishment of the klotho gene product is potentially useful in treating emphysema.
2.Establishment of PCR system for sequencing the human klotho gene.
The primer sets were designed for PCR in order to determine the DNA sequences of the human klotho gene.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 須賀 達夫: "老化モデルマウス(klothoマウス)と肺気腫"Annual Review呼吸器2002. 43-51 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 須賀 達夫: "動物モデルにおける実験的肺気腫"現代医療. 34・9. 69-73 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 須賀 達夫: "klotho遺伝子異常と肺気腫、呼吸器疾患関連遺伝子異常"分子呼吸器病. 7・6. 11-13 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suga, Tatsuo: "The animal model of aging (klotho mouse) and pulmonary emphysema."Annual Review Kokyuki 2002. 43-51 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suga, Tatsuo: "Experimental pulmonary emphysema in animal models."Gendaiiryo. 34-9. 69-73 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suga, Tatsuo: "Mutation of the klotho gene and pulmonary emphysema"RESPIRATORY MOLECULAR MEDICINE. 7-6. 88-90 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 須賀 達夫: "老化モデルマウス(klothoマウス)と肺気腫"AnnualReview呼吸器2002. 43-51 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 須賀 達夫: "動物モデルにおける実験的肺気腫"現代医療. 34・9. 69-73 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 須賀 達夫: "klotho遺伝子異常と肺気腫、呼吸器疾患関連遺伝子異常"分子呼吸器病. 7・6. 11-13 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 須賀 達夫: "klotho遺伝子欠損マウスは肺気腫を発症する:出生後の肺構造保持の役割"日本呼吸器学会雑誌. 40・3. 203-209 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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