2002 Fiscal Year Final Research Report Summary
EXPERMENTEAL STUDY ON THE CDNTROL OF PULMONARY FIBROSIS BY ENHANCING HGF/c-MET SYSTEM
| Project/Area Number |
12670549
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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 | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
TANAKA Ryoichi THE UNIVERSITY OF TOKYO, ALLERGY AND RHEUMATOLOGY, ASSOCIATE PROFESSOR, 医学部附属病院, 助手 (60272556)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kazuhiko THE UNIVERSITY OF TOKYO, ALLERGY AND RHEUMATOLOGY, PROFESSOR, 医学部附属病院, 教授 (80191394)
DOHI Makoto THE UNIVERSITY OF TOKYO, ALLERGY AND RHEUMATOLOGY, ASSOCIATE PROFESSOR, 医学部附属病院, 助手 (60222155)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Hepatocyte Growth Factor / Transforming Growth Factor β-1 / Bleomycin / Pulmonary Fibrosis / Repair |
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| Research Abstract |
1. STUDY ON ENDOGENEOUS HGF EXPRESSION IN A MOUSE MODEL OF PULMONARY FIBROSIS
We investigated on the role of endogeneous Hepatocyte Growth Factor (HGF) in lung injury and repair. According to our pilot study and other previous reports, approximately 50 days after the bleomycin instillaton, bleomycin-induced pulmonary fibrosis resolves considerably in its histologic findings. The content of hydroxyproline, a marker of collagen amount in lung also reaches plateau. We hypothesized that the expression of HGF should be upregulated at that time, as HGF is an important growth factor for repair. Bleomycin was administered intratracheally to induce lung fibrosis. Lungs were cut out on Days 3, 7, 14, 28, 42, 56 and 84. Then the lungs were used for histologic study, HGF protein measurement by ELISA, hydroxyproline measurement. Some lungs were used for extraction of RNA followed by RT-PCR and assay of gene expression. Endogeneous HGF in bleomycin-administered lungs increased until Day 14, and peaked as much as 2.6 times higher than that in the control lungs. It decreased thereafter, but remained 1.8 times higher than control value still on Day 84, which suggested that repair process of lung was on-going still at that time. Hydroxyproline content was sharply increased from Day 7 and reached 1.3 times higher than the control value on Day 28. It still increased gradually to 1.5 times higher than control value on Day 84. This findings showed that fibrotic change was still progressing as late as Day 84,though it is very slow.
2. STUDY ON ENDOGENEOUS TGFβ-1 EXPRESSION IN A MOUSE MODEL OF PULMONARY FIBROSIS
We measured TGFβ-1 content, a marker of lung fibrosis, in bronchoalveolar lavage fluid (BALF) at some time periods. It peaked on Day 7 and showed the similar change to the lung HGF. The ratio of HGF/TGF β-1 content in BALF was significantly inversely correlated with the Hydroxyproline content in lungs.
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