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Analysis of the cytoprotective effect of STAT3 on pulmonary epithelial cell injury

STAT3对肺上皮细胞损伤的细胞保护作用分析

基本信息

批准号：
15590808
负责人：
YOSHIDA Mitsuhiro
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590808/
关键词：
Pulmonary epithelial cell STAT3 Hyperoxia Bleomycin Apotosis Pulmonary fibrosis Lung injury 肺胞上皮細胞肺障害 stat3

项目摘要

ObjectiveSTAT3 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 questionResults.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 activation2 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.

目的STAT3首先被发现是介导白介素6(IL-6)作用的信号分子。最近的研究表明，它具有细胞保护作用。然而，目前尚不清楚它是否也对肺上皮细胞具有细胞保护作用。本研究项目就是为了澄清这个问题而进行的。IL-6对过氧化氢应激诱导的肺上皮细胞A549死亡具有保护作用，且呈剂量依赖关系。这种作用是通过STAT3激活来实现的。2将肺上皮细胞中STAT3表达完全缺失的肺特异性STAT3基因敲除小鼠用于高氧实验。这些基因敲除小鼠的存活率低于野生型小鼠。组织学研究显示，这些基因敲除小鼠的肺上皮细胞死亡明显。肺特异性STAT3基因敲除小鼠用于博莱霉素实验。与野生型小鼠相比，这些基因敲除小鼠的肺部纤维化变化更严重。这些基因敲除的小鼠的存活率也降低了。结论：STAT3对多种应激所致的肺上皮细胞损伤具有保护作用。提示肺上皮细胞中STAT3的激活可能是肺纤维化等肺损伤的一种治疗策略。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stat-3 is required for pulmonary homeostasis during hyperoxia.

DOI：
10.1172/jci19491
发表时间：
2004
期刊：
The Journal of clinical investigation
影响因子：
0
作者：
I. Hokuto;M. Ikegami;Mitsuhiro Yoshida;K. Takeda;S. Akira;A. Perl;W. Hull;S. Wert;J. Whitsett
通讯作者：
I. Hokuto;M. Ikegami;Mitsuhiro Yoshida;K. Takeda;S. Akira;A. Perl;W. Hull;S. Wert;J. Whitsett

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