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Molecular mechanisms of alveolar epithelial healing process in acute lung injury

Research Project

Project/Area Number 12470322
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 Faculty of Medicine

Principal Investigator

SUGAWARA Kazuhiro  University of the Ryukyus, Faculty of Medicine, Professor, 医学部, 教授 (20171126)

Co-Investigator(Kenkyū-buntansha) OHSHIRO Masakatsu  University of the Ryukyus, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (00315483)
MIYATA Yuji  University of the Ryukyus, Faculty of Medicine, Assistant, 医学部, 助手 (60315471)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2000: ¥9,500,000 (Direct Cost: ¥9,500,000)
Keywordsacutelunginjury / wound healing / cytokines / molecular biology / in situ hybridization / apoptosis / growth factor / 虚血性脳障害 / 遅発性神経細胞死
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 induced the alveolar epithelial cell proliferation and increased surfactant protein mRNAs, and 3) intratracheal instillation of KGF prevented acute lung injury by bleomycin and HC1. To clarify the mechanism that KGF prevents lung injury and fibrosis by bleomycin and HC1, 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 on acute lung injury, which C/EBPα is more expressed in endotoxin lung inj … More ury, 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 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/EBPa may play a key role in the proliferation of alveolar type II cells and the gene regulation of surfactant proteins. 3. 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. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kazuhiro Sugahara et al.: "Surfactant protein gene expression in acute lung injury and repair"J Jpn Med Soc Biol Interface. 32. 26-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomohiro Sadohara et al.: "Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hppocampal CA1 field of the gerbil brain"NeuroReport. 12. 71-76 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiro Sugahara et al.: "C/EBPδ is expressed in alveolar type II cells and may regulate surfactant protein genes"Am J Respir Crit Care Med. 163. A741-A741 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiro Sugahara et al.: "The roles of alveolar type II epithelial cells in acute lung injury and repair"Ryukyu Med J. 20. 161-166 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiro Sugahara et al.: "Mice lacking CCAAT/enhancer binding protein (C/EBP)α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs"Cell & Tissue Res. 306. 57-63 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Manabu Kakinohana et al.: "Propofol reduces spinal motor neuron excitability in humans"Anesth & Analg. 94(In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 須加原 一博: "『TEXT麻酔・蘇生学』第2版"南山堂. 493 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kakinohana,M. et al.: "Propofol reduces spinal motor neuron excitability in humans"Anesth & Analg. 94 (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugahara,K. et al.: "Surfactant protein gene expression in acute lung injury and repair"J Jpn Med Soc Biol Interface. 32. 26-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sadohara,T. et al.: "Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hippocampal CA1 field of the gerbil brain"NeuroReport. 12. 71-76 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugahara,K. et al.: "C/EBP5 is expressed in alveolar type II cells and may regulate surfactant protein genes"Am J Respir Crit Care Med. 163. A741-A741 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugahara,K. et al.: "Mice lacking CCAAT/ enhancer binding protein )C/EBP)α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs"Cell & Tissue Res. 306. 57-63 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugahara,K. et al.: "The roles of alveolar type II epithelial cells and may regulate surfactant protein genes"Ryukyu Med J. 20. 161-166 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugahara,K. et al.: "Mice lacking CCAAT/ enhancer binding protein )C/EBP)alpha have increased alveolar epithelial cell proliferation and surfactant protein mRNAs"Mol Biol Cell. 12. 228a-228a (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuda,R., Sugahara,K. et al.: "Comparative effect of amrinone, aminophylline and diltiazem on rat smooth muscle"Acta Anaesthesiol Scand. 44. 763-766 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhiro Sugahara et al.: "Surfactant protein gene expression in acute lung injury and repair"J Jpn Med Soc Biol Interface. 32. 26-31 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomohiro Sadohara et al.: "Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hippocampal CA1 field of the gerbil brain"NeuroReport. 12. 71-76 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "C/EBPδ is expressed in alveolar type II cells and may regulate surfactant protein genes"Am J Respir Crit Care Med. 163. A741-A741 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "The roles of alveolar type II epithelial cells in acute lung injury and repair"Ryukyu Med J. 20. 161-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "Mice lacking CCAAT/enhancer binding protein (C/EBP)α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs"Cell & Tissue Res. 306. 57-63 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Manabu Kakinohana et al.: "Propofol reduces spinal motor neuron excitability in humans"Anesth & Analg. 94(In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 須加原 一博: "『TEXT麻酔・蘇生学』第2版"南山堂. 493 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al: "C/EBPδ is expressed in alveolar type II cells and may regulate surfactant protein genes"Am J Respir Crit Care Med. 163(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al: "Keratinocyte growth factor prevents ischemia-induced delayed neuronal death in the hippocampal CA1 field of the gerbil brain"NeuroReport. 12. 71-76 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "Expression of CCAAT/ enhancer binding protein family members and regulation of surfactant proteins in the lungs"J Jpn Med Soc Biol Interface. 31. 75-76 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fumihiko Matsuda et al.: "Comparative effect of amrinone, aminophylline and diltiazem on rat airway smooth muscle"Acta Anaesthesiol Scand. 44. 763-766 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "Keratinocyte growth factor (KGF) is expressed in the hippocampal neurons and attenuates ischemia-induced delayed neuronal death"Mol Biol Cell. 11. 309a-309a (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Sugahara et al.: "C/EBPδ is expressed only in some alveolar type II cells, and C/EBPα may have inhibitory regulation on SP-C genes"Am J Respir Crit Care Med. 161. A121-A121 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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