| Project/Area Number |
08670682
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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 |
Respiratory organ internal medicine
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| Research Institution | TOKYO WOMEN'S MEDICAL COLLEGE |
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Principal Investigator |
ISHIHARA Yoko TOKYO WOMEN'S MEDICAL COLLEGE,DEPT.HYGENE AND PUBLIC HEALTH,ASSOCIATE PROFESSOR, 医学部, 講師 (50203021)
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| Co-Investigator(Kenkyū-buntansha) |
KOHRI Kazuhiro TOKYO WOMEN'S MEDICAL,DEPT OF INTERNAL MEDICINE (I), ASSISTANT, 医学部, 助手 (60287315)
NAGAI Atsushi TOKYO WOMEN'S MEDICAL COLLEGE,DEPT OF INTERNAL MEDICINE (I), PROFESSOR, 医学部, 教授 (60101820)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | MOLECULAR CHAPERONE / HSP47 / PULMONARY FIBROSIS / PULMONARY EMPHYSEMA / BLEOMYCIN / CIGARETTE SMOKING / TNF-alpha OVEREXPRESSION TRANSGENIC MICE / HEART SHOCK PROTEIN / ヒートショックプロテイン / コラーゲン / TGF-β / コラーゲン特異的シャペロン / トランスジェニックマウス / ブレオマイシン肺臓炎 |
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| Research Abstract |
This work was investigated the expression and regulation of collagen specific molecular chaperone HSP47 in pulmonary emphysema and fibrosis, using bleomycin-treated mice, long term cigarette smoke-exposed mice and TNF-alpha overexpression pulmonary-fibrosis transgenic (Tg) mice.
Bleomycin-treated mice showed increase of lung hydroxyproline contents from week 4, and reached to a maximum at week 12 after administration. HSP47 gene expression was increased a transient at week 4 and 5 after treatment, but at week 12, compared with the control group. On the other hand, lung HSP47 gene did not show any marked changes during long term cigarette smoke-exposed mice (from day 4 to month 12) compared with the control group. Tg mice showed HSP47 gene suppression at 5 mo of age, this tendency was also observed at 1 year of age compared with same age of non-Tg mice. Pulmonary function pattern, the degree of fibrotic lesion in morphological findings, and lung hydroxyproline contents also reached to a maximum at 4-5 mo of age, and then this levels were maintained until over 1 year of age. Collagen typ IV gene expression in Tg mice paralleled HSP47 gene expression rather than collagen type (I) and (III). Total elastolytic activity in bronchoalveolar lavage showed a slight increase, whereas MMP-1 gene was expressed at from 1 to 4 mo of age in Tg mice compared with the non-Tg group. TGF-beta gene over expression was not observed during experimental period in the Tg mice.
Above results suggest that HSP47 gene may be related to the progressive of non-reversible pulmonary fibrosis, but not as a trigger of fibrosis. However, we could not define the relationship between HSP47 gene and pulmonary emphysema in the experiment model. Collergen deposition could be regulated by control of HSP47 gene in the progressive pulmonary fibrosis.
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