1999 Fiscal Year Final Research Report Summary
Molecularbiological analysis of human fetal lung development and its clinical application
| Project/Area Number |
09671196
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Keio University |
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Principal Investigator |
IKEDA Kazushige Keio University, School of Medicine, Department of Pediatrics, Instructor, 医学部・小児科, 助手 (00193194)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUMURA Mituaki Keio University, School of Medicine, Department of Pediatrics, Instructor, 医学部・小児科, 助手 (70172153)
SATO Seiji Keio University, School of Medicine, Department of Pediatrics, Assistant Professor, 医学部・小児科, 専任講師 (80146638)
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| Project Period (FY) |
1997 – 1999
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| Keywords | TTF-1 / HNF-3 / intrauterine MRI / SSFSE / nitrofen / fetal lung / pulmonary hypoplasia / SP-B |
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| Research Abstract |
1. TTF-1 is a prerequisite transcription factor for intrauterine lung development, We analyzed cis-element of human TTF-1 gene. 3 kb of TTF-15' region is required for lung selective expression of TTF-1 gene, and HNF-3β upregulate TTF-1 gene transcription in vitro, We made 3 kb human TTF-1 promoted luciferase transgenic mice. Luciferase activity was detected in both lung and brain, This finding shows that 3 kb of TTF-15' region is not enough for lung specific expression in vivo,
2. We presented a case of twin who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology, Intrauterine MRI using SSFSE provides the possibility of diagnosing hypoplastic lungs prenatally.
3. Nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) causes fetal lung hypoplasia without cingenital diaphragmatic defects, when fed to pregnant mice to Day 9 of gestation. Intratracheal administration of perfluorocarbon resulted in lung expansion and prolonge
… More
d survival of nitrofen induced lung hypoplasia. Perfluorocarbon may be useful in stabilizing critically in infants with pulmonary hypoplasia during the early phase of their therapy.
4. We assessed maturation of pulmonary epithelial cells of human fetuses at 21 weeks of gestation. Immunohistochemical analysis showed SP-B proprotein was detected both bronchioles and terminal airways. However, mature SP-B peptide positive cells were very few. Transmission electron microscopy showed intracellular glycogen granules were still rich and lamellar bodies were few. These findings means the processing from SP-B preproprotein to mature peptide is immature at 21 weeks of gestation.
5. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B+/ gene-targeted mice and wild-type SP-B+/+ littermates were exposed to hyperoxia or room air. Although specific lung compliance in room air in SP-B+/ mice was slightly reduced as compared with that in SP-B+/+ mice, it was reduced more markedly during hyperoxia. Increased alveolar-capillary leakage and relative deficiency of SP-B may contribute to oxygen-induced pulmonary dysfunction in SP-B+/ mice. These data support the concept that SP-B plays an important protective role in the lung. Less
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