Project/Area Number |
08457409
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
|
Research Institution | Kumamoto 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)
|
Keywords | acute 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.
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