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Investigation of molecular mechanism in the development of chronic obstructive pulmonary disease (COPD) and susceptibility to cigarette smoke-induced lung injury using transgenic animal models.

Research Project

Project/Area Number 16590734
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, ASSISTANT PROFESSOR, 医学部, 助手 (50334115)

Co-Investigator(Kenkyū-buntansha) KURABAYASHI Masahiko  GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 医学系研究科, 教授 (00215047)
NAGAI Ryozo  TOKYO UNIVERSITY HOSPITAL, PROFESSOR, 医学部付属病院, 教授 (60207975)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAnimal model of chronic obstructive pulmonary disease (COPD) / klotho gene / klotho mutant mice / klotho mutant rats / pulmonary emphysema
Research Abstract

1.Phenotypes of klotho transgenic rats
(1)Systolic blood pressure in transgenic rats was similar to wild-type rats.
(2)Microscopic findings showed no significant difference in the aorta, the heart, and the kidney between wild-type and transgenic rats.
(3)Endothelial-dependent relaxation of the aorta in response to acetylcholine was significantly ameliorated in transgenic rats as compared with wild-type rats.
(4)A decrease in urinary excretion of nitric oxide metabolites was observed in transgenic rats as compared to wild-type rats. Urinary excretion of isoprostane was reduced in transgenic rats as compared with wild-type rats.
(5)Hydroethidine, an oxidative fluorescent dye, was used to evaluate the level of superoxide in situ. Superoxide production is decreased in klotho transgenic rats as compared to wild-type.
2.Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice
To investigate the ability of klotho gene expression to regulate the development of ageing-related disorders, we established an inducible klotho gene expression system using homozygous mutant klotho mice. Mice carrying an exogenous klotho gene fused to the mouse metallothionein-I promoter, in which klotho gene expression was dependent on zinc water feeding.
We demonstrate that many advanced ageing-like phenotypes of homozygous mutant klotho mice were restored to normal whenever klotho gene expression was induced. Conversely, decreasing klotho gene expression in these rescued homozygous mutant klotho mice induced several ageing-like phenotypes.
Our data indicate that klotho gene expression may be effective in the treatment of multiple age-related disorders and is essential for maintaining animals free of these disorders.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (2 results)

All 2005

All Journal Article (2 results)

  • [Journal Article] Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice2005

    • Author(s)
      Hiroaki Masuda
    • Journal Title

      Mech Ageing Dev 126・12

      Pages: 1274-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice2005

    • Author(s)
      Hiroaki Masuda, Hirotaka Chikuda, Tatsuo Ssuga, Hiroshi Kawaguchi, Makoto Kuro-o
    • Journal Title

      Mech Ageing Dev 126-12

      Pages: 1274-1283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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