2001 Fiscal Year Final Research Report Summary
Role of matrix metalloproteinase-2 in bleomycin-induced pulmonary fibrosis
| Project/Area Number |
12670582
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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, Professor, 医学部, 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) |
2000 – 2001
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| Keywords | MMP-2 / KO mice / bleomycin / alveolar epithelial cells / migration of epithelial cells / intraalveolar fiborsis / alveolar bronchiolization / gelatin zymography |
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| Research Abstract |
Fibrosis in interstitial pneumonia is usually formed in intraalveolar spaces and covered by regenerated alveolar or bronchogenic epithelial cells. In addition to that, activated MMP-2 is suggested to be important to the process of alveolar repair in interstitial pneumonia and the alveolization in fetal lungs. In this context, we investigated the bleomycin lungs in MMP-2 KO and wild mice. After intratracheal administration of bleomycin to mice, animals were sequentially sacrificed. Electron microscopic studies and immunohistochemistry for MMP-2, keratin, PCNA, fibronectin were performed. The degree of fibrosis was quantified by Ashcroft's method and the amount of hydroxyproline in lung tissues. Active form of MMP-2 of lung homogenates was analyzed with Western blotting and gelatin zymography. Degree of fibrosis was similarly observed in both KO and wild mice. Type II alveolar epithelial cell coverage on intraalveolar fibrosis was markedly less observed in KO mice, though the rate of proliferation of alveolar epithelial cells was similar in KO and wild mice. The initial detachment of alveolar epithelial cells from basement membrane and the migration may be blocked in KO mice. Intraalveolar fibrosis in KO mice was mainly mural incorporation and obliteration types, but bud type was less prominent than wild mice, because of retarded alveolar epithelial cell coverage on intraalveolar fibrosis. Alveolar bronchiolization in MMP-2 KO mice was formed similarly to wild mice, although it is reported that the bronchiolization was blocked in MMP-9 KO mice.
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