| Project/Area Number |
15390262
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
KEICHO Naoto International Medical Center of Japan, Department of respiratory Diseases, Director, 呼吸器疾患研究部, 部長 (80332386)
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| Co-Investigator(Kenkyū-buntansha) |
HIJIKATA Minako International Medical Center of Japan, Department of respiratory Diseases, Division leader, 呼吸器疾患研究部, 室長 (90332387)
NAKATA Koh Niigata University Medical and Dental Hospital, Life Science Medical Center, Professor, 医歯学総合病院生命科学医療センター, 教授 (80207802)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | chronic airway inflammation / airway defense mechanism / genetic polymorphism / mucin / airway epithelial cell / 気管支上皮細胞気相・液相培養 / ヒト気管支上皮細胞気相・液相培養 |
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| Research Abstract |
We identified genetic polymorphisms related to pathogenesis of chronic airway inflammation and infection and involved in airway defense mechanism. We conducted disease association studies and analyzed functional significance of the genetic polymorphisms. Identified polymorphisms included MUC1, 2, 4, SAC, 5B and 8 in the airway mucin family and DEFB1 and DEFB2 in the beta-defensin family. Intron polymorphisms of CFTR causing exon 9 skipping were also investigated. One of the polymorphisms in the promoter region of the MUC5B gene was associated with diffuse panbronchiolitis, one of the typical chronic airway diseases and the resistant allele suppressed the transcriptional activity of the gene. Furthermore, aberrant expression of MUC5B was observed in the airway epithelial cells of the disease, but not in the normal lung. One of the promoter haplotype of the DEFB1 gene has strong transcriptional activity of the gene, which was parallel with the resistant allele showing resistance to fungus infection by a previous disease association study. 5T allele located in intron 8 of CFTR gene causes exon 9 skipping and we found its frequency was 1 to 2% in Japanese population.
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