| Project/Area Number |
09670632
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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 | Nippon Medical School |
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Principal Investigator |
FUKUDA Yuh Nippon Medical School, Department of Pathology, Associate professor, 医学部, 助教授 (60097037)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAKI Masamichi Nippon Medical School, Department of Pathology, Associate professor, 医学部, 助教授 (40096954)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | pulmonary fibrosis / bleomycin / regenerating epithelial cells / MMP / MT-MMP / TIMP / gelatin zymography / BAL / ブレオマイシン / 線維芽細胞 / IV-型コラーゲン |
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| Research Abstract |
In pulmonary fibrosis, there are idiopathic pulmonary fibrosis which shows irreversible fibrosis and poor prognosis, and others which show reversible fibrosis and good prognosis. In this study, we investigated the role of metalloproteinases (MMP) which is important enzyme in the metabolism of extracellular matrices in bleomycin-induced pulmonary fibrosis in rabbit which is known to be reversible model. In the early stage, intraalveolar fibrosis was made, these fibrosis adhere to the alveolar walls and obliterate the alveolar spaces, and the alveolar structures were remodeled. These fibrosis was covered by the regenerated bronchiolar and alveolar epithelial cells. In later stage, fibrotic area was decreased in size and alveolar structures were reconstructed in association with the regeneration of alveolar epithelial cells. Immunohistochemical study revealed that MMP-l, MMP-2, MMP-9 and their inhibitor (TIMP)-2 were mainly localized in the regenerating epithelial cells. In addition to that, membrane type (MT-i) MMP which is known to be only one factor to activate MMP-2 in vivo was detected in the regenerating epithelial cells. Gelatin zymography of lung tissue homogenates showed significant increases of MMP-2 land the ratio of active formlinactive form MMP-2 in later stage of this model. Bronchoalveolar lavage fluid (BALF) also showed the significant increases of MMP-2 and the ratio of active formfinactive form MMP-2 in the later stage. It was suggested that MT-i MMP produced by the regenerating epithelial cells participates the activation of MMP-2 in vivo. We consider that the significant increase of the ratio of active form/inactive form MMP 2 in the fibrotic lesions may facilitate the process of the repair in the fibrotic lungs. It is also suggested that the possibility of the application of the gelatin zymography in BALF of the patients with pulmonary fibrosis.
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