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Molecular mechanisms of alveolar epithelial healing process in acute lung injury

Research Project

Project/Area Number 14370492
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

SUGAHARA 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)
TOKUMINE joho  University of the Ryukyus, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70274909)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2002: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordsacute lung injury / wound healing / cytokines / molecular biology / in situ hybridization / apoptosis / growth factor / 骨髄幹細胞 / 急性肺傷害
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 induced the alveolar epithelial cell proliferation and increased surfactant protein mRNAs, and 3)intratracheal instillation of KGF prevented acute lung injury by bleomycin and HCl.To clarify the mechanism that KGF prevents lung injury and fibrosis by bleomycin and HCl, 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/EBPct and C/EBPδ are reciprocal expressions on acute lung injury, which C/EBPα is more expressed in endotoxin lung injury, and … More 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/EBPct 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. We injected stem cells transvenously into the bleomycin treated rats. We found the alveolar epithelial cells which are injected stem cells. 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. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] T.Ohshiro, K.Sugahara, et al.: "Effects of antenatal vitamin A on lung maturation and incidence of congenital diaphragmatic hernia in the nitrofen of rats"J Jpn Med Soc Biol Interface. 34. 54-55 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Ohshiro, K.Sugahara, et al.: "Antenatal treatment with vitamin A reduces the incidence of nitrofen-induced congenital diaphragmatic hernia but decreases lung growth"Am J Respir Crit Care Med. 167. A383-A383 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J Tokumine, T Ohshiro, K Sugahara: "Transvenous implantation of bone marrow stromal cells to bleomycin-induced lung injury model in rats"Molecular Biology of the Cell. 14. L334-L334 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Tokumine, K.Sugahara, et al.: "Spinal GDNF levels is increased after transient spinal cord ischemia in the rat"Acta Neurochirurgica Suppl. 86. 231-234 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Sasara, D Cizkova, R Mestril, J Galik, K Sugahara, et al.: "Spinal heat shock protein (70) expression : effect of spinal ischemia, hyperthermia (42 C)/hypothermia (27 C),NMDA receptor activation"Neurochemistry International. 44(1). 53-64 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S Nakamura, M Kakinohana, K Sugahara, et al.: "Intrathecal morphine but not buprenorphine or pentazocine, can induce spastic paraparesis after noninjurious interval of spinal cord"Anesth & Analg. 98(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kuroiwa, A.Baethmann, et al.: "Brain Edema XII"Springer Wien New York, Austria. 609 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Oshiro, K Sugahara et al.: "Effects of antenatal vitamin A on lung maturation and incidence of congenital diaphragmatic hernia in the nitrofen model of rats."J Jpn Med Soc Biol Interface. 34. 54-55 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Oshiro, K Sugahara et al.: "Antenatal treatment with vitamin A reduces the incidence of nitrofen induced congenital diaphragmatic hernia but decreases lung growth."Am J Respir Crit Care Med. 167. A383-A383 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J Tokumine, T Oshiro, K Sugahara et al.: "Transvenous implantation of bone marrow stromal cells to bleomycin-induced lung injury model in rats."Mol Biol Cell. 14. L334-L334 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J Tokumine, K Sugahara et al.: "Spinal GDNF level is increased after transient spinal cord ischemia in the rat."Acta Neurochirur. Suppl86. 231-234 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Sasara, D Cizkova, R Mestril, L Galik, K Sugahara et al.: "Spinal heat shock protein(70)expression : effect of spinal ischemia, hyperthermia(42 C)/hypothermia(27 C), NMDA receptor activation."Neurochemistry Int. 44(1). 53-64 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S Nakamura, M Kakinohana, K Sugahara et al.: "Intrathecal morphine but not buprenorphine or pentazocine, can induce spastic paraparesis after noninjurious interval of spinal cord."Anesth & Analg. 98(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Kuroiwa, A Baethmann et al.: "Brain Edema XII"Springer Wien New York. 609 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Oshiro, K.Sugahara, et al.: "Effects of antenatal vitamin A on lung maturation and incidence of congenital diaphragmatic hernia in the nitrofen model of rats"J Jpn Med Soc Biol Interface. 34. 54-55 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Oshiro, K.Sugahara, et al.: "Antenatal treatment with vitamin A reduces the incidence of nitrofen-induced congenital diaphragmatic hernia but decreases lung growth"Am J Respir Crit Care Med. 167. A383-A383 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J Tokumine, T Oshiro, K Sugahara: "Transvenous implantation of bone marrow stromal cells to bleomycin-induced lung injury model in rats"Molecular Biology of the Cell. 14. L334-L334 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Tokumine, K.Sugahara, et al.: "Spinal GDNF level is increased after transient spinal cord ischemia in the rat"Acta Neurochirurgica Suppl. 86. 231-234 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T Sasara, D Cizkova, R Mestril, J Galik, K Sugahara, et al.: "Spinal heat shock protein (70) expression : effect of spinal ischemia, hyperthermia (42 C)/hypothermia (27 C), NMDA receptor activation"Neurochemistry International. 44(1). 53-64 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] S Nakamura, M Kakinohana, K Sugahara, et al.: "Intrathecal morphine but not buprenorphine or pentazocine, can induce spastic paraparesis after noninjurious interval of spinal cord"Anesth & Analg. 98(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Kuroiwa, A.Baethmann, et al.: "Brain Edema XII"Springer Wien New York, Austria. 609 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Nakamura, K.Sugahara, et al.: "Effect of GABA agents on morphine induced spastic paraparesis after a non-injurious interval of spinal cord ischemia in rats"Anesthesia & Analgesia. 94. 1389-1395 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Oshiro, K.Sugahara, et al.: "Effects of vitamin A and growth factors on the lung of drug-induced congenital diaphragmatic hernia (CDH)"J Jpn Med Soc Biol Interface. 33. 67-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Sugahara, et al.: "Effects of vitamin A and growth factors on hypoplastic lungs in congenital diaphragmatic hernia in rats"Molecular Biology of the Cell. 13. 532a-532a (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Sugahara, et al.: "The roles of alveolar type II epithelial cells in inflammation and repair process of acute lung injury"J Jpn Med Soc Biol Interface. 33. 5-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] J.Tokumine, K.Sugahara, et al.: "Spinal GDNF level is increased after transient spinal cord ischemia in the rat"Acta Neurochirurgica Suppl. 85(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Oshiro, K.Sugahara, et al.: "Antenatal treatment with vitamin A reduces the incidence of nitrofen-induced congenital diaphragmatic hernia but decreases lung growth"Am J Respir Crit Care Med. 167(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kuroiwa, et al.: "Brain Edema XII"Springer-Verlag Wien (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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