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In vivo transfer of an extracellular domain of platelet-derived growth factor beta gene by HVJ-liposome method ameliorated bleomycin-induced pulmonary fibrosis.

Research Project

Project/Area Number 08457181
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HAYASHI Seiji  Osaka University Medical School, Depariment of Medicine III,Assistant Professor, 医学部, 講師 (70218577)

Co-Investigator(Kenkyū-buntansha) 細江 重人  大阪大学, 医学部・第三内科, 助手 (60263274)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsHVJ-liposome / Pulmonary Fibrosis / In vivo gene transfer / platelet-derived growth factor / platelet-derived growth factor receptor / bleomycin / 間質性肺炎 / サイトカイン / PDGF / 可溶性PDGF受容体 / TGF-β
Research Abstract

Platelet-derived growth factor (PDGF) is one of the most potent mitogens and chemoattractants for a variety of mesenchymal cells. A number of investigators have reported augmented expression of PDGF in the lung with IPF and other pulmonary fibrosis. To accomplish regulation of PDGF activity, we constructed an expression plasmid of the extracellular domain of PDGF receptor beta chain (XR), which lacks intracellular tyrosine kinase domain and transmembrane portions, and we estimated the therapeutic effects of the XR gene transfer through trachea on bleomycin-induced lung fibrosis of C57BL/6 mice by using hemagglutinating virus of Japan (HVJ)-liposome method. The transfer of the XR gene improved the increase in the wet weight, hydroxyproline content and histopathologic change of the lung that was induced by bleomycin. These findings suggested that PDGF playd a crucial role in the pathogenesis of pulmonary fibrosis, and the XR gene by using the HVJ-liposome method may limit the progression of pulmonary fibrosis.

Report

(2 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] 吉田 光弘、他: "生体内遺伝子導入によるTGF-bおよびPDGFの肺線維症における病態解析" 日本臨床. 14. 418-422 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 林 清二、他: "気道肺胞上皮細胞へのin vivo遺伝子導入-間質性肺炎の病態解析" 医学のあゆみ. 176. 677-681 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 林 清二、他: "肺線維症とサイトカイン:in vivo遺伝子導入による病態解析" Molecular Medicine. 33. 192-199 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 林 清二: "TGF-β" KEY WORD 1996-‘97 呼吸器系. 150-151 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 林 清二、他: "遺伝子導入法による間質性肺炎の病態解析と治療への応用" 分子呼吸器病. 1. 22-28 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 林 清二、他: "肺線維症とサイトカイン-in vivo遺伝子導入による病態解析" 日本胸部疾患学会雑誌. 34. 150-154 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira, M.et al.: "Idiopathic Pulmonary Fibrosis : Progression of Honeycombing at Thin-Section CT." Radiology. 189. 687-691 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Carrington CB,et al.: "Natural history and treated course of usual and desquamative interstitial pneumonia." New Engl.J.Med.298. 801-809 (1978)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wright, P.H., et al: "Criptogenic fibrosing alveolitis : Assessment by graded trephine lung biopsy histology compared with clinical, radiographic, and physiological features." Br.J.Dis.Chest.75. 61-70 (1981)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fabisiak, J.P., et al.: "Platelet-derived growth factor, in Cytokines of the Lung" J.Kelley Editor.Marcel Dekker : New York.3-39 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaoka, I., et al.: "Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis." J.Clin.Invest.85. 2023-2027 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Antoniades, H.N., et al.: "Platelet-derived growth factor in idiopathic pulmonary fibrosis." J Clin Invest.86 (4). 1055-64 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shaw, R.J., et al.: "Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF (B) gene activation and up-regulation by interferon gamma." Am Rev Respir Dis.143 (1). 167-73 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Martinet, Y., et al.: "Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with odiopathic pulmonary fibrosis." N.Engl.J.Med.317. 202-209 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Walsh, J., M.et al: "Variable expression of platelet-derived growth factor family proteins in acute lung injury." Am J Respir Cell Mol Biol.9 (6). 637-44 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Liu, J.Y., et al.: "Rapid activation of PDGF-A and -B expression at sites of lung injury in asbestos-exposed rats." Am J.Resir.Cell.Mol.Biol.17. 129-140 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yi, E.S., et al.: "Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo." Am J Pathol.149 (2). 539-48 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshida, M., et al.: "A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor b1, or platelet-derived growth factor B gene." Proc.Natl.Acad.Sci.USA.92. 9570-9574 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Duan, D.-S.R., et al.: "A functional soluble extracellular region of the platelet-derived growth factor (PDGF) b-receptor antagonizes PDGF-stimulated responses." J Biol Chem.266. 413-418 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kato, K., et al.: "Expression of hepatitis B virus surface antigen in adult rat liver. Co-introduction of DNA and nuclear protein by a simplified liposome method." J.Biol.Chem.266 (6). 22071-22074 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneda, Y., K.et, al.: "Introduction and expression of the human insulin gene in adult rat liver." Science (Washi.DC). 243. 375-378 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gray, K., et al.: "Coordinate regulation by diethylstibestrol of the platelet-derived growth factor-A and -B chains and the PDGF receptor a- and b-subunits in the mouse uterus and vagina : potential mediators of estrogen action." Endocrinology. 136. 2325-2340 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bidwell, M., et al.: "Analysis of messenger ribonucleic acid and protein for the ligands and receptors of the platelet-derived growth factor signaling pathway in the placenta, extraembryonic membranes, and uterus during the latter half of murine gestation." Endocrinology. 136. 5189-5201 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Woessner, J.F., at al: "The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid.Arch.Biochemical." Biophys. 93. 440-447 (1961)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haynes, A.R., et al.: "Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells." Am J Respir Cell Mol Biol.72 (2). 198-206 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Siegbahn, A., et al.: "Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes." J.Clin.Invest.85. 916-920 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Maeda, A., et al.: "Increased expression of platelet-derived growth factor A and insulin-like growth factor-I in BAL cells during the development of bleomycin-induced pulmonary fibrosis in mice." Chest.109 (3). 780-6 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Remick, D.G., et al.: "Cyclosporin inhibits TNF production without decreasing TNF mRNA levels." Biochem.Biophys.Res.Commun.161. 551-555 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bochner, B.S., et al.: "Interleukin lproduction by human lung tissue. II.Inhibition by anti-inflammatory steroids." J.Immunol.139. 2303-2307 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Eiji Takeuchi et al.: "Lung cancer producing interleukin-6." Internal Medicine. 35. 212-214 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miki Takagi et al.: "Interleukin-6 seceting phaeochromocytoma associated with clinical markers of inflammation." Clin.Endocrinol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kiyoshi Nishioka et al.: "Epidemiological analysis of prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc)." J Dermatol.23. 677-682 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 吉田光宏、林清二: "生体内遺伝子導入によるTGF-βおよびPDGFの肺線維症における病態解析" 日本臨床. 54. 418-422 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 林清二 他: "気道肺胞上皮細胞へのin vivo遺伝子導入-間質性肺炎の病態解析" 医学のあゆみ. 176. 677-681 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 林清二 他: "遺伝子導入法による間質性肺炎の病態解析と治療への応用" 分子呼吸器病. 1. 22-28 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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