| Project/Area Number |
13670604
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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 | Kyushu University |
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Principal Investigator |
KUWANO Kazuyoshi University Hospital lecutrer, 医学部附属病院, 講師 (40205266)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Masaki University Hospital assistant, 医学部附属病院, 助手 (50325461)
HAGIMOTO Naoki Graduate School of Medical Sciences, assistant, 大学院・医学研究院, 助手 (50315074)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | ubiquitin / proteasome / lung injury / pulmonary fibrosis / apoptosis / p53 / MDM2 / SUMO1 |
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| Research Abstract |
Ubiquitin-proteasome system in lung injury and fibrosis
Ubiquitin and multiubiquitin were upregulated in lung tissues from patients with idiopathic pulmonary fibrosis (IPF). There were apoptotic epithelial cells in lung tissues from IPF. Multiubiquitin was detected in lung epithelial cells of bleomycin-induced pulmonary fibrosis in mice. Proteasome inhibitor induced apoptosis in lung epithelia cells in vitro, in which multiubiquitin was detected in apoptotic cells. Multiubiquitin was also detected by western blot analysis. These results suggest that epithelial cell apoptosis is involved in lung injury and pulmonary fibrosis in mouse and human, and that malfunction of ubiquitin-proteasome system may be involved in this apoptosis.
The interaction of p53, MDM2, and SUMO1 in lung injury and fibrosis
The expression of p53, MDM2, and SUMO1 were upregulated in lung epithelial cells from patients with IPF and from bleomycin-induced pulmonary fibrosis in mice. The upregulation of these proteins were also detected by western blot analysis. MDM2 is E3 ligase for p53 and degenerate through ubiqutination. SUMO1 regulates self-ubiquitination of MDM2. We found that p53, MDM2 and SUMO1 interact each other and degrade through ubiquitin-proteasome system in lung epithelia cells. Ubiquitin-proteasome system is involved in p53-induced apoptosis of lung epithelial cells.
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