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Molecularbiological analysis of human fetal lung development and its clinical application

Research Project

Project/Area Number 09671196
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKeio University

Principal Investigator

IKEDA Kazushige  Keio University, School of Medicine, Department of Pediatrics, Instructor, 医学部・小児科, 助手 (00193194)

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)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsTTF-1 / HNF-3 / intrauterine MRI / SSFSE / nitrofen / fetal lung / pulmonary hypoplasia / SP-B / サーファクタント蛋白 / 肺上皮細胞 / 肺サーファクタント / 肺の発達
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

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Ikeda K, Shaw-White JR Wert SE, Whitsett JA: "Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells"Molecular and Cellular Biology. 16. 3626-3636 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokieda K, Whitesett JA, Clark JC, Weaver TE, Ikeda K, McConnell KB, Jobe Ah, Ikegami M, Iwamoto HS: "Pulmonary dysfunction in neonatal SP-B-deficient mice"American J. of Physiology. 237. L875-L882 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokieda K, Iwamoto HS, Bachurski C, Wert SE, Hull WM, Ikeda K, Whitsett JA: "SP-B deficient mice are susceptible to hyperoxic injury"American J of Respiratory Cell and Molecular Biology. 21. 463-472 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K, Hayashida S, Hokuto I, Tokieda K, Tanigaki S, Tanaka M,: "Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs"J of Perinatal Medicine. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 池田一成、吉岡博史、古庄知己、森和宏、林田慎哉、時枝啓介、田中守、宮越敬、福澤龍二: "胎児肺上皮細胞におけるthyroid transcription factor-1(TTF-1)の発現に関する免疫組織学的検討-SP-B、SP-Cとの比較-"日本新生児学会雑誌. 34. 324 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 池田一成、森和宏、時枝啓介、林田慎哉、古庄知己、田中守、石本人士: "パラフィン切片を利用した肺上皮細胞のmaturationの評価-8種類の抗体による免疫組織学化学的検討-"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K, Shaw-White JR, Wert SE, Whitsett JA: "Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells"Mol Cell Biol. 16(7). 3626-3636 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokieda K, Whitsett JA, Clark JC, Weaver TE, Ikeda K, McConnell KB, Jobe AH, Ikegami M, Iwamoto HS: "Pulmonary dysfunction in neonatal SP-B-deficient mice."Am J Physiol. 273(4Pt 1 ). L875-L882 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokieda K, Iwamoto HS, Bachurski C, Wert SE, Hull WM, lkeda K, Witsett JA: "SP-B deficient mice are susceptible to hyperoxic injury."American J of Respiratory Cell and Molecular Biology. 21(4). 463-472 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K, Mori K, Hayashida S, Hokuto I, Tokieda K, Tanigaki S, Tanaka M: "Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs"J of Perinatal Medicine. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K, Yoshihashi H, Kosyo T, Mori K, Hayashida S, Tokieda K, Tanaka M, Miyakoshi K, Fukuzawa R: "Immuohistochemical analysis of thyroid transcription -1(TTF- 1) expression in fetal pulmonary epithelial cells - comparison with SP-B and SP-C -"Acta. Neonat. Jpn. 34. 324 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K, Mori K, Tokieda K, Hayashida S, Kosho T, Tanaka M, Ishimoto H: "Evaluation of pulmonary epithelial cells maturation - immunohistochemical analysis of eight different antibodies using paraffin embedded section-"Acta. Neonat. Jpn. 35. 274 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda K,Hokuto I,Mori K,Hayashida S,Tokieda K,Tanigaki S,Tanaka M,Yuasa Y: "Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs"Journal of Perinatal Medicine. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokieda K,Iwamoto HS,Bachurski C,Wert SE,Hull WM,Ikeda K,Whitsett JA: "SP-B deficient mice are susceptible to hyperoxic injury"American J of Respiratory Cell and Molecular Biology. 21・4. 463-472 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokieda K.Iwamoto HS.Bachurski C Wert SE.Hull WM Ikeda K.Whitsett JA: "SP-B deficient mice are susceptible to hyperoxic injury" American J of Respiratory Cell and Molecular Biology. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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