2004 Fiscal Year Final Research Report Summary
Analysis of the cytoprotective effect of STAT3 on pulmonary epithelial cell injury
| Project/Area Number |
15590808
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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 | Osaka University |
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Principal Investigator |
YOSHIDA Mitsuhiro Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90359844)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Toru Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80346212)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Pulmonary epithelial cell / STAT3 / Hyperoxia / Bleomycin / Apotosis / Pulmonary fibrosis / Lung injury |
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| Research Abstract |
Objective
STAT3 was first discovered as a signal molecule which mediated the effects of Interleukin-6 (IL-6). Recent studies have revealed that it has a cytoprotective effect. However, it remains still unclear whether it is also cytoprotecitve for pulmonary epithelial cells. This research project has been done to clarify this question
Results.
1. IL-6 has a cytoprotective effect onpulmonary epithelial cell A549 death induced by hydrogen peroxide stress in a dose dependent manner. This effect is mediated via STAT3 activation
2 Lung specific STAT3 knockout mice in which STAT3 expression in pulmonary epithelial cell is exclusively deficient was used for hyperoxia experiments. The survival rate of these knockout mice was low tempered with that of wild type mice. Histological studies revealed that pulmonary epithelial cell death was prominent in these knockout mice.
3. Lung specific STAT3 knockout mice was used for bleomycin experiments. Fibrotic changes were more severe in the lungs of these knockout mice tempered to those of wild type mice. Survival rate was also decreased in these knockout mice. Apoptosis of Pulmonary epithelial cells was involved in the mechanisms of the prominent pulmonary fibrosis in these knockout mice.
Conclusions.
These findings demonstrate that STAT3 has a cytoprotective effect on pulmonary epithelial cell injury induced by several stress. This result suggests that STAT3 activation in the pulmonary epithelial cells could be a therapeutic strategy for lung injury such as pulmonary fibrosis.
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Research Products
(4 results)
