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Molecular analyses of hypoxia response of pulmonary arterial endothelium by using genetic engineering

Research Project

Project/Area Number 09670629
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SETOGUCHI Yasuhiro  Juntendo University school of Medcine, Assistant, 医学部, 助手 (90206649)

Co-Investigator(Kenkyū-buntansha) 岡 正彦  順天堂大学, 医学部, 助手 (60203965)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsendothelium / hypoxia / pulmonary hypertension / cis-element / gene transfer / adenoviurs vector / 遺伝子導入 / アプリウイルスベクター / シスエレメント / アデノウイルスベクター / 低酸素性肺高血圧 / 低酸素応答 / HIF / ベクター / 内皮細胞 / 分子生物 / 遺伝子工学
Research Abstract

[Purpose] Hypoxia-inducible factor I (HW-1) is originally identified as a nuclear factor that is induced by hypoxia and bound to a site in the erythropoietin (Epo) hypoxia-response element (HRE). HIF-1 plays an important role in 02 homeostasis by activating transcription of genes whose' products mediate essential cellular and systemic response to hypoxia, including erythropoiesis, glycolysis, vasculogenesis, and vasodilatation. The aim of this study is to clarify hypoxia response of pulmonary arterial (PA) endothelium by addition of genetic modification to secrete reporter gene (Re) product following adenovirus-mediated transfer of both Re cDNA and hypoxia response cis-element. [Method] To evaluate hypoxia response of PA endothelium, two type of adenovirus vector were constructed. One adenovirus vector contains Re expression cassette with hypoxia response cis element (HRE) isolated from Epo genome (AdHRE), and the other one is adenovirus vector containing Re expression cassette without … More HRE (Ad) as control vector. Using these vectors, hypoxia response of PA endothelium, aortic endothelium was evaluated by using the ratio of production of Re product in exposure to hypoxia and normoxia. [Results) Each Ad treated-endothelium exposed to hypoxia had no increase in the ratio of Re production, compared with Ad treated endothelium in normoxia. In marked contrast, AdHRE-infected PA endothelium exposed to hypoxia had an increase in the ratio of Re production, 4 fold compared with AdHRE infected PA endothelium in normoxia (p<O.OOl). Furthermore, interestingly, AdHRE infected endothelium in distal PA exposed to hypoxia had a significantly large increase in the ratio of Re production, 2 fold compared with AdHRE infected endotbeliuxn in proximal PA exposed to hypoxia (p<O.OOl). To evaluate hypoxia response in different type of endothelium, aortic endothelium was exposed to hypoxia following treatment with AdHERE.AdHRE-treated-aortic endothelium has a plateau in the ratio of Re production 12 hrs following the exposure to hypoxia, 4 or 2 fold compared with AdHRE-treated each endothelium in normoxia. [Conclusion] Analysis system of hypoxia response was established by using adenovirus-mediated transfer of hypoxia response cis element. Our current study using this HRE transfer system demonstrated that hypoxia response of PAE showed larger than that of AE of systemic circulation, especially endothelium in distal PA relevant to vascular remodeling had a markedly larger hypoxia response. This HRE- gene transfer system was feasible to evaluate disorder of hypoxia response in circulatory or pulmonary diseases. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Y.Setoguchi: "Human vasceelar-endothelial cells have diverse hypoxia response in HIF-dependent manner" Am J.Respir Crit Care Med. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Osada: "Gene therapy forcenal anemia in mice with polycystic lcidney using an adenovirus vector encoding the human enythropoietiv gene" Kidney International. 55(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Mogi: "Efficient generation of autologous peripheral blood derived cytotoxic Tlywphoceetes against morly immunogenic human tumars" Clin Cancer Res. 4. 713-720 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Kitagawa: "Induction of DNA fragmentation and HSP72 immunoreadivit by adenovirus-mediated gene transfer in normal gerbi hippocampus and ventricle" J.Neurosci Res. 54. 38-45 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Warita: "Expression of adenovirus-mediated E.cditacz gene in sreletal muscles and spinal morter neurons of transgenic mice" Neurosci Lett. 246. 153-156 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Abe: "Temporal Profile of adenovirus-mediated E.coli lacz gene expression in norwal and post ischemic gerbile hippocampus" Neurol Res. 20. 689-696 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Setoguchi Y., Koiwai Y., Kodama Y., Fukuchi Y.: "Human vascular endothelial cells have diverse hypoxia-response in HIF-dependent manner." Am J Respir Crit Care Med. (Inpress). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osada S,Ebihara and Setoguchi Y.: "Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus vector encoding the human erythropoietin gene" Kidney Intern. 55 (Inpress). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mogi S,Ebata T,Setoguchi Y,Fujime M,Heike Y,Kohsaka T,Yagita H,Okumura K and Azuma M.: "Efficent generation of autologous peripheral blood-derived cytotoxic T lymphocytes against poorly immunogenic human tumors using recombinant CD80-adenovirus together with interleukin 12 and interleukin 2" Clin Cancer Res. 4. 713-720 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitagawa H,Setoguchi Y,Fukuchi Y,Mitsumoto Y,Koga N,Mori T and A.K.: "Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus-mediated gene transfer in normal gerbil hippocampus and ventricle." J Neurosci Res. 54. 38-45 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Warita H., Abe K,Setoguchi Y.and Itoyama Y.: "Expression of adenovirus-mediated E.coli LacZ gene in skeletal muscle and spinal motor neurons of transgenic mice with a mutant superoxide dismutase gene." Neurosci Let. 246. 153-156 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe K,Kitagawa H and Setoguchi.Y.: "Temporal profile of adenovirus-mediated E.coli LacZ gene expression in normal and post-ischemic gerbil hippocampus and ventricle." Neurol Res. 20. 689-696 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitagawa H,Setoguchi Y,Fukuchi Y,Mitsumoto Y,Koga N,Mori T and A.K.: "DNA fragmentation and HSP72 gene expression by adenovirus-mediated gene transfer in postischemic gerbile hippocampus and ventricle." Metab Brain Dis. 13. 211-223 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe K,Setoguchi Y,Hayashi T and I.Y.: "In vivo adenovirus-mediated gene transfer and expression in ischemic and reperfused rat brain." Brain res. 763. 191-201 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe K., Setoguchi Y., T.Hayashi, Y.Itoyama.: "Dissociative expression of adenoviral-mediated E.coli LacZ gene between ischemic and reperfused rat brain." Neurosci Let. 226. 53-56 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Setoguchi: "Human vascular endothelial cells have diverse hypoxia-response in HIF-dependent manner" Am. J.Respir. Crit Care Med. in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Osada: "Gene therapy for reral anemia in mice wiht polycystic kidney using an adenovirus vector encoding the human enythropoietin gene" Kidney International. 55. in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Mogi: "Efficlent generation of autologous peripheral blood derived cytotoxic Tlymphocytes against poorly immunogenic human tumors" Clin Cancer Res. 4. 713-720 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kitagawa: "Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus-mediated gene transfer in normal gerbilhippocampu and ventricle" J Neurosci Res. 54. 38-45 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Warita: "Expression of adenovirus-mediated E.col ; LacZ gene in Skeletal muscles and spinal moter neurons of transgenic mice" Neurosci Lett. 246. 153-156 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe K: "Temporal profile of adenovirus-mediated E.coi ; LacZ gene expression in normal and post ischemic gerbile hippocampus and ventricle" Neurol Res. 20. 689-696 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tamaki Y, Setoguchi Y, et al: "Amelioration of pulmonary hypertension byusing transfer of ceNOS cDNA into airway" Am J Respir Crit Care Med. 155. A442 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Abe K, Setoguchi Y, et al: "In vivo adenovirus-mediated gene transfer and expression in ischemic and reperfused rat brain" Brain Res. 763. 191-203 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Abe K, Setoguchi Y, et al: "Dissociative expression of adenoviral-medrited E.cdilacZ gene between ischemic and reperfused rat brain" Neurosci Let. 226. 53-56 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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