| Project/Area Number |
10670755
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Saitama Medcal School |
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Principal Investigator |
OSHIKA Eiki Saitama Medical School, Department of Pediatrics, Assistant Professor, 医学部, 講師 (80260842)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Ieaki Saitama Medical School, Department of Pediatrics, Assistant Professor, 医学部, 助手 (80271237)
MITSUBAYASHI Takashi Saitama Medical School, Department of Pediatrics, Assistant Professor, 医学部, 講師 (00174079)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Bronchial Asthma / Rat / Growth Factor / Keratinocyte Growth Factor / Hepatocyte Growth Factor / Surfactant Protein |
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| Research Abstract |
We have investigated possible roles of keratinocyte growth factor (KGF)and hepatocyte growth factor (HGF) in lung morphogenesis. Trsnscripts for both KGF and its receptor were detected early and their abundance increased during lung morphogenesis by polymerase chain reaction. Exogenous KGF increased the expression of surfactant protein C mRNA in cultured rat lung. But, HGF had no significant effects to cultures of fetal lung explants. Next, we examined the effects of dexamethasone (DEX) and retinoic acid (RA) on airway branching and subsequent lung maturation. The DEX treated lung had that the transcript levels of several genes related to epitherial growth (KGF, KGF receptor and hepatocyte growth factor receptor) and differentiation (sturfactant protein, SP-A, SP-B and SP-C and Clara cell secretory protein, CC-10) were precociously increased. Our results showed that DEX treatment of the lung during the early pseudoglandular stage accelerates the acquisition of several features of advanced maturation that normally accompany late stages of fetal development. RA at 10^<-4> M inhibited branching and dilated the distal tubules and caused dilation of the proximal tubules destined to form the trachea and the main bronchi. The adverse effects of DEX were all prevented by RA.In addition, RA inhibited several features of DEX-induced accelerated maturation. We postuate that KGF mediates at least some effects of DEX on lung maturation and gene expression. Also, we postuate that normal lung development requires a balanced action of endogeneous retinoids and glucocorticoids.
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