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Molecular mechanisms of alveolar epithelial healing process in acute lung injury

Research Project

Project/Area Number 18390430
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionUniversity of the Ryukyus

Principal Investigator

SUGAHARA Kazuhiro  University of the Ryukyus, Faculty of Medicine, Professor (20171126)

Co-Investigator(Kenkyū-buntansha) TOKUMINE Joho  University of the Ryukyus, University Hospital, Assistant Professor (70274909)
OSHIRO Masakatsu  University of the Ryukyus, University Hospital, Instructor (00315483)
SAIKAWA Satoko  University of the Ryukyus, University Hospital, Instructor (20404569)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,510,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordsacute lung injury / wound healing / cytokines / alveolar epithelial cells / growth factor / transcription factor / molecular biology / bone marrow stem cell / 急性肺障害
Research Abstract

1. The inhibition of acute lung injury by growth factors for alveolar type II cells: We have demonstrated that 1) keratinocyte growth factor (KGF) is a potent factor for proliferation and differentiation for alveolar type II cells, 2) intratracheal instillation of KGF prevented acute lung injury by bleomycin and HCI. To clarify the mechanism that KGF prevents lung injury and fibrosis by bleomycin and HCI, we examined expressions of the transcription factors C/EBP, HGF, and TGF on acute lung injury by bleomycin, endotoxin and KGF stimulation. C/EBP family members are differentially expressed in acute lung injury. C/EBPδ is expressed in some alveolar type II cells only, which suggests the existence of the subtypes of alveolar type II cells. C/EBPα and C/EBPδ are reciprocal expressions, which C/EBPα is more expressed in endotoxin lung injury, and C/EBPδ is more expressed in bleomycin lung fibrosis.
2. The regulation of surfactant protein mRNAs by transcription factor C/EBP: We examined the … More expression of surfactant protein mRNAs on the lungs from C/EBPα-deficient and C/EBPβ-deficient mice. Mice lacking C/EBPα showed pulmonary abnormality resembling alveolar proteinosis and have died of respiratory failure within several hours after birth. Immunohistochemical and in situ hybridization analyses revealed that positive cells for SP-A and SP-C were abundant, and expression of SP-A, SP-B and SP-C mRNAs were increased in the lungs of newborn C/EBPα-deficient mice, compared to those of control mice. Thus, these results suggest that C/EBPα may play a key role in the proliferation of alveolar type II cells and the gene regulation of surfactant proteins.
3. Lung stem cells from bone marrow derived cells of GFP rats. We injected stem cells transvenously into the bleomycin treated rats. We found the alveolar epithelial cells which are green and stained with SP-A & SP-C. These cells may be important for repairing process of lung injury.
4. We have examined whether KGF prevents another organ injury, transient brain ischemia-induced delayed neuronal death in hippocampal region in gerbils. We have demonstrated that KGF mRNA is observed in the neuronal cells of hippocampus and amygdala, and KGF has a protective effect against ischemic hippocampal neuronal damage. We also demonstrated the effect of ethyl pyruvate on spinal cord ischemia in rats. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 6 results) Presentation (5 results) Book (3 results)

  • [Journal Article] Transcranial motor-evoked potentials monitoring can detect spinal cordischemia more rapidly than spinal cord evoked potentials monitoring during aortic occlusion in rats.2007

    • Author(s)
      Kakinohana M, et al
    • Journal Title

      European Spine Journal 16

      Pages: 767-793

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of iandiolol on mechanical and metabolic changes in rat reperfused ischemic hearts.2007

    • Author(s)
      Sakanashi M, et al
    • Journal Title

      Clinical & Experimental Pharmacology & Physiology 43

      Pages: 55-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord evoked potentials monitoring during aortic occlusion in rats.2007

    • Author(s)
      Kakinohana M, et al
    • Journal Title

      European Spine Journal 16

      Pages: 767-793

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of landiolol on mechanical and metabolic changes in rat reperfused ischemic hearts.2007

    • Author(s)
      Sakanashi M, et al
    • Journal Title

      Clinical & Experimental Pharmacology & Physiology 43

      Pages: 55-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Intravenous infusion of dexmedetomidine can prevent the degeneration of spinal ventral neurons induced by intrathecal morphine after a noninjurious interval of spinal cord ischemia in rats.2007

    • Author(s)
      Kakinohana M, et al
    • Journal Title

      Anesthesia & Analgesia 105

      Pages: 1086-1093

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Transcranial motor-evoked potentials monitoring can detect spinal cord ishemia more rapidly than spinal cord evoked potentials monitoring during Aortic occlusion in rats.2007

    • Author(s)
      Kakinohana M, et. al.
    • Journal Title

      European Spine Journal 16

      Pages: 767-793

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravenous infusion of dexmedetomidine can prevent the degeneration of Spinal ventral neurons induced by intrathecal morphine after a noninjurious Interval of spinal cord ischemia in rats.2007

    • Author(s)
      Kakinohana M, et. al.
    • Journal Title

      Anesthesia & Analgesia 105

      Pages: 1086-1093

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of landiolol on mechanical and metabolic changes in rat reperfused ischemic hearts.2007

    • Author(s)
      Sakanshi M, et. al.
    • Journal Title

      Clinical & Experimental Pharmacology & Physiology 16

      Pages: 55-60

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of landiolol on mechanical and metabolic changes in rat perfused ischemic hearts.2007

    • Author(s)
      Sakanashi M, et al.
    • Journal Title

      Clinical & Experimental Pharmacology & Physiology 43

      Pages: 55-60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly then spinal cord-evoked potentials…2007

    • Author(s)
      Kakinohana M, et al.
    • Journal Title

      European Spine Journal 15 (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Alveolar epithelial cells : differentiation and lung injury2006

    • Author(s)
      Sugahara K, et al
    • Journal Title

      Respirology 11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Alveolar epithelial cells: differentiation and lung injury.2006

    • Author(s)
      Sugahara K, et al
    • Journal Title

      Respirology 11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Alveolar epithelial cells : differentiation and lung injury.2006

    • Author(s)
      Sugahara K, et al.
    • Journal Title

      Respirology 11

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Influence of the descending thoracic aortic cross clamping on bispectral index value and plasma propofol concentration in humans.2006

    • Author(s)
      Kakinohana M, et al.
    • Journal Title

      Anesthesiology 104

      Pages: 939-943

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of ethyl pyruvate against-injurious spinal cord ischemia in rats.2006

    • Author(s)
      Sugahara K, et al.
    • Journal Title

      Critical 10

      Pages: 180-180

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differentiation of bone marrow stromal cells into alveolar epithelial cells in the lungs of bleomycin-induced injury rata model.2006

    • Author(s)
      Sugahara K. et al.
    • Journal Title

      Proceedings of the American thoracic Society 2006 3

    • Related Report
      2006 Annual Research Report
  • [Presentation] Central venous-arterial carbon dioxide difference can not correlate with cardiac index in the cardiac surgery.2007

    • Author(s)
      Haga A, et al
    • Organizer
      Annual meeting of the Society of Cardiovascular Anesthesiologists
    • Place of Presentation
      Montreal, Quebec, Canada
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Landiolol improves ischemiareperfusion cardiac injury independently of antioxidative effect.2007

    • Author(s)
      Sakanashi M, et al
    • Organizer
      8^<th> Congress of the European Association for Clinical Pharma- cology and Therapeutics
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Landiolol improves ischemia-repertusion cardiac injury independently of Antioxidative effect.2007

    • Author(s)
      Sakanashi M, et. al.
    • Organizer
      European Association for Clinical Pharmacology & Therapeutics
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2007 Annual Research Report
  • [Presentation] Differentiation of bone marrow stromal cells into alveolar epithelial cells inthe lungs of bleomycin-induced injury rat model.2006

    • Author(s)
      Sugahara K, et al
    • Organizer
      2006 International Conference of the American Thoracic Society
    • Place of Presentation
      San Diego, California, U.S.A.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Differentiation of bone marrow stromal cells into alveolar epithelial cells in the lungs of bleomycin-induced injury rat model.2006

    • Author(s)
      Sugahara K, et al
    • Organizer
      2006 International Conference of the American Thoracic Society
    • Place of Presentation
      San Diego, California, U.S.A.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 麻酔科学レビュー20082008

    • Author(s)
      須加原一博
    • Total Pages
      266
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 麻酔科学レビュー20082008

    • Author(s)
      須加原 一博
    • Total Pages
      266
    • Publisher
      総合医学社
    • Related Report
      2007 Annual Research Report
  • [Book] 超音波ガイド下中心静脈穿刺法マニュアル2007

    • Author(s)
      須加原一博
    • Total Pages
      107
    • Publisher
      総合医学社
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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