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2003 Fiscal Year Final Research Report Summary

Reorganization of alveolar capillaries in pulmonary fibrosis by gene trasfection of Hepatocyte Growth Factor

Research Project

Project/Area Number 14570534
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

EBINA Masahito  Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (10280885)

Co-Investigator(Kenkyū-buntansha) KIKUCHI Toshiaki  Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (10280926)
Project Period (FY) 2002 – 2003
Keywordspulmonary fibrosis / alveolar capillaries / bleomycin / gene therapy / hepatocyte growth factor
Research Abstract

Hepatocyte growth factor (HGF), a pluripotent mediator with anti-fibrotic effects, is a candidate gene therapy for idiopathic pulmonary fibrosis for which current therapy is minimally effective. We examined human 11(hHGF) gene transfer by a unique gene delivery system using macroaggregated albumin-polyethylenimine conplex (MM-PEI). which induces lung specific gene expression without causing inflammation. lntravenous administration of MAA-PEI with 1 μg pCAG.hHGF (MAA-PEI+pCAG.hHGF) to C57BL/6 mice induced a level of hHGF expression in the lung equal to 10 μg of pCAG.hHGF alone, prolonged its expression only in the lung, and reduced the hHGF express ion in other organs. In situ RT-PCR revealed hHGF production in endothelial cells, alveolar macrophages, and alveolar epithelial cells, but not in airway epithelial cells. Inflammatory cytokines (TNF-α and IL-6) and collagen synthesis in the lungs after bleomycin injury were statistically decreased by MAA-PEI+pCAG.hHGF injection. Since regeneration of alveolar epithelial cells and capillary endothelial cells by bone marrow-derived stem cells after bleomycin-induced injury was unaffected by HGF, the primary anti-inflammatory and anti-fibrotic mechanism of HGF after lung injury is likely to be the inhibition of apoptosis, as suggested by in vitro experiments. These results indicate that this novel HGF gene transfer system may have promising clinical applications.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Ebina M, et al.: "Heterogeneous Increase of CD34-positive Alveolar Capillaries in Idiopathic Pulmonary Fibrosis."Am J Respir Crit Care Med. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizugawa M, et al.: "Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin."Am J Physiol. 284. L526-L532 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ebina M, Shimizukawa M, et al.: "Heterogeneous Increase in CD34-positive Alveolar Capillaries in Idiopathic Pulmonary Fibrosis"Am J Respir Crit Care Med. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizukawa M, Ebina M, et al.: "Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin"Am J Physiol. 284. L526-L532 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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