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Role of alveolar epithelial cell proliferation and surfactant protein in acute lung injury : effect of KGF and artificial surfactant on lung injury

Research Project

Project/Area Number 08457409
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKumamoto University

Principal Investigator

SUGAHARA Kazuhiro  Kumamoto University School of Medicine, Associate Professor, 医学部, 助教授 (20171126)

Co-Investigator(Kenkyū-buntansha) TASHIRO Masafumi  Kumamoto University School of Medicine, Assistant, 医学部・附属病院, 助手 (60264305)
SAKANASHI Yuji  Kumamoto University School of Medicine, Assistant, 医学部, 助手 (30274707)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordsacute lung injury / alveolar epithelial cells / lung fibrosis / growth factor / wound healing / surfactant / cytokines / in situ hybridization
Research Abstract

1.Effect of growth factor for alveolar type II cells on lung injury : We have demonstrated that keratinocyte growth factor (KGF) is a potent factr for proliferation and differentiation of alveolar type II cells (Am J Physiol 269,1995). We have examined whether KGF would prevent bleomycin-induced lung injury and fibrosis. Recombinant human KGF (rhKGF) was injected intratracheally at 48h before and 24h after bleomycin. KGF treatment prevents 1)loss of body weight, 2)reduced total lung capacity, 3)accumulation of collagen type I & III and thier mRNAs, and 4)decreased autoradiographic silver grains for surfactant protein A (SP-A), SP-B and SP-C mRNAs in the rat lungs induced by bleomycin. Lung injury due to acid instillation was also prevented by KGF pretreatment at 72h before acid (0.1N HC1) instillation, but not by posttreatme2) nt. 2.Combined posttreatmental effects of KGF and artificial surfactant on lung injury : The combined instillations of KGF and artificial surfactant 48h after bleomycin or acid didn't change lung injury so much because of the strong pulmonary edema. Therefore, we were examining the better time point of instillation for preventing lung injury, with artificial surfactant. 3.To clarify the mechanisms of prevention, we were examining the expression of the transcription factor, C/EBP family members, and the lungs of C/EBP deficient mice. 4.Prevention of lung injury due to intratracheal instillation of cultured alveolar cells : We are under experiments on whether cultured alveolar epithelial cells stimulated by KGF wouldprevent lung injury and fibrosis. 5.Future project : We are going to study gene transfer of KGF using adeno-virus intratracheally for preventing lung injury and fibrosis.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] K.Sugahara, et al.: "Double intratracheal instillations of keratinocyte growth factor prevent bleomycin-induced lung fibrosis in rats demonstrated by immunohistochemistry and in situ hybridization." Journal of Pathology. 184(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Sugahara, et al: "NADH-diaphorase deficiency was identified in the patient with congenital methaemoglobinemia detected by pulse oximetry." Intensive Care Medicine. 24(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Sugahara, et al.: "Effects of soluble factors and extracellular matrix on DNA synthesis and surfactant gene expression in primary cultures of rat alveolar type II cells." Cell & Tissue Research. 291. 295-303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Sugahara, et al.: "Roles of the transcriptional factor,C/EBP family members in acute lung injury and in C/EBPα deficiency mice." Am.J.Respir.Crit.Care Med. 157(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Nakano, et al.: "Differential expression of α1(IV),α2(IV),α5(IV),α6(IV) collagen chains in the basement membrane of normal breast,benign and malignant breast diseases." Mol,Biol.Cell. 8. 179a-179a (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Sugahara, et al.: "Differential expression of the transcription factor,C/EBPα,β,and δ in lung injury and fibrosis in rats." Am.J.Respir.Crit.Care Med.155. A696-A696 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al.: "Dverexpression of surfactant protein SP-A,SP-B and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury." Laboratory Investigation. 74. 209-220 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al.: "Role of alveolar epithelial proliferation and surfactant protein in acute lung injury." J.Jpn.Med.Soc.Biol.Interface. 26. 101-113 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al.: "Keratinocyte growth factor (KGF) prevents bleomycin-induced lung fibrosis in rats." Am.J.Respir.Crit.Care Med.153. A642-A642 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 須加原 一博 他: "Keratinocyte growth factor (KGF)による肺胞上皮細胞の増殖、分化と肺サーファクタント・アポ蛋白遺伝子発現動態" 日本界面医学会雑誌. 27. 151-153 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 須加原 一博: "ARDSにおける肺胞上皮細胞の増殖・分化と肺サーファクタント・アポ蛋白質遺伝子発現動態" 日本臨床. 54. 61-65 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 須加原 一博: "Annual Review呼吸器 1996" 中外医学社(東京), 256 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Double intratracheal instillation of keratinocyte growth factor prevent bleomycin-induced lung fibrosis in rats demonstrated by immunohistochemistry and in situ hybridization." J Pathol. 184 ; (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Effects of soluble factors and extracellular matrix on DNA synthesis and surfactant gene expression in primary cultures of rat alveolar type II cells." Cell Tissue Res. 291. 295-303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Roles of the transcription fact or, C/EBP family members in acute lung injury and in C/EBP alpha deficient mice." Am J Respir Crit Care Med. 157 ; (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakano, S., et al: "Differential expression of alpha1 (IV), alpha2 (IV), alpha5 (IV), alpha6 (IV), collagen chains in the basement membrane of normal breast, benign and malignant breast diseases." Mol Biol Cell. 8. 179a-179a (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yano, T., et al: "Keratinocyte growth factor growth factor modulates the surfactant protein expression after acid instillation in rat lungs." J Jpn Med Soc Biol Interface. 28. 59-62 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Differential expression of the transcription factor, C/EBP-a, beta and delta in lung injury and fibrosis." Am J Respir Crit Care Med. 155. A696-A696 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Overexpression of surfactant protein SP-A,SP-B and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury." Lab Invest. 74. 209-220 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Role of alveolar epithelial proliferation and surfactant protein in lung injury." J Jpn Med Soc Biol Interface. 26. 101-113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Keratinocyte growth factor (KGF) prevents bleomycin-induced lung fibrosis in rats." Am J Respir Crit Care Med. A642-A642 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K., et al: "Role of keratinocyte growth factor (KGF) on alveolar epithelial prolifertion and surfactant protein gene expression in vitro and in vivo." J Jpn Med Soc Biol Interface. 27. 151-153 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugahara, K.: Recent study on alveolar type II epithelial cells. Annual Review KOKYUUKI 1996, Edited by S.Kudo. TYUUGAIIGAKUSYA(TOKYO), 26-35 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Sugahara, et al.: "Double intratracheal instillations of keratinocyte growth factor prevent bleomycin-induced lung flbrosis in rats demonstrated by immunohistochemistry and in situ hybridization." Journal of Pathology. 184(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Sugahara, et al.: "NADH-diaphorase deficiency was identified in the patient with congenital methaemoglobinemia detected by pulse oximetry." Intensive Care Medicine. 24(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Sugahara, et al.: "Effects of soluble factors and extracellular matrix on DNA synthesis and surfactant gene expression in primary cultues of rat alveolar type II Cells." Cell & Tissue Research. 291. 295-303 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Sugahara, et al.: "Roles of the transcriptional factor, C/EBP family members in acute lung injury and in C/EBPα deficiency mice." Am. J. Respir. Crit. Care Med. 157(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Nakano, et al.: "Differential expression of α1(IV), α2(IV), α5(IV), α6(IV) collagen chains in the basement membrane of normal breast, benign and malignant breast diseases." Mol. Biol. Cell. 8. 179a-179a (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Sugahara, et al.: "Differential expression of the transcription factor, C/EBP α, β, and δ in lung injury and fibrosis in rats." Am. J. Respir. Crit. Care Med.155. A696-A696 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugahara, K et al: "Differential expression of the rtranscription factor, C/EBP-and in lung injury and fibrosis in rats." Am. J. Respir. Crit. Care Med.155(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugahara, K., et al.: "Overexpression of surfactant protein SP-A, SP-B and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury." Laboratory Investigation. 74. 209-220 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugahara, K, et al.: "Role of alveolar epithelial proliferation and surfactant protein in acute lung injury." J. Jpn. Med. Soc. Biol. Interface. 26. 101-113 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugahara, K, et al.: "Keratinocyte growth factor (KGF) prevents bleomycin-induced lung fibrosis in rats." Am. J. Respir. Crit. Care Med.153. A642-A642 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 須加原一博他: "Kerastinocyte growth factor(KGF)による肺胞上皮細胞の増殖、分化と肺サーファクタント・アポ蛋白遺伝子発現動態" 日本界面医学会雑誌. 27. 151-153 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 須加原一博: "ARDSにおける肺胞上皮細胞の増殖・分化と肺サーファクタント・アポ蛋白質遺伝子発現動態" 日本臨床. 54. 61-65 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 須加原一博: "Annual Review呼吸器 1996" 中外医学社(東京), 256 (1996)

    • Related Report
      1996 Annual Research Report

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

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