Analysis of the cytoprotective effects of Bcl-xL on pulmonary epithelial cell injury

Bcl-xL对肺上皮细胞损伤的细胞保护作用分析

• 批准号: 17590789
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590789/
• 关键词: Bcl-xL; pulmonary epitheial cell; hydrogen peroxide; lung injury; bleomycin; Bc1-xL; 肺胞上皮細胞; 肺線維症; アポトーシス

ObjectiveBcl-xL was first discovered as a molecule related with apoptotic pathway. 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. Bleomycin injured pulmonary epithelial cell MLE15 cells in a dose dependent manner. Knockdown of Bcl-xL expression using a specific siRNA for Bcl-xL increased this pulmonary epithelial cell injury induced by bleomycin.2. Hydrogen peroxide injured MLE15 cells in a dose dependent manner. Knockdown of Bcl-xL expression using a specific siRNA for Bcl-xL increased this pulmonary epithelial cell injury induced by low dose of hydrogen peroxide, but not by high dose of hydrogen peroxide.3. We made lung specific Bcl-xL knockout mice in which Bcl-xL expression in pulmonary epithelial cell is exclusively deficient. These knockout mice grew up normally. Histological studies revealed that lung structure was normal in these knockout mice.Conclusions.These findings demonstrate that Bcl-xL is not necessary for lung development and growth, but that Bcl-xL has cytoprotective effects on pulmonary epithelial cell injury induced by several stress. These results suggest that Bcl-xL in the pulmonary epithelial cells could be a therapeutic strategy for lung injury such as pulmonary fibrosis.

Bcl-xL是最早发现的一种与细胞凋亡相关的分子。最近的研究表明，它具有细胞保护作用。然而，它是否对肺上皮细胞也有细胞保护作用仍不清楚。本研究旨在阐明这一问题。博莱霉素对肺上皮细胞MLE 15细胞的损伤呈剂量依赖性。使用针对Bcl-xL的特异性siRNA敲低Bcl-xL表达增加了博来霉素诱导的肺上皮细胞损伤。过氧化氢对MLE 15细胞的损伤呈剂量依赖性。使用针对Bcl-xL的特异性siRNA敲低Bcl-xL表达增加了低剂量过氧化氢诱导的肺上皮细胞损伤，但不增加高剂量过氧化氢诱导的肺上皮细胞损伤.我们建立了肺特异性Bcl-xL基因敲除小鼠，其中肺上皮细胞中的Bcl-xL表达完全缺失。这些基因敲除小鼠正常生长。组织学研究表明，肺结构是正常的，在这些敲除mice.Conclusions.These研究结果表明，Bcl-xL是不必要的肺发育和生长，但Bcl-xL有细胞保护作用的肺上皮细胞损伤诱导的几个压力。这些结果表明，肺上皮细胞中的Bcl-xL可能是肺损伤如肺纤维化的治疗策略。

项目成果

IL-10 Inhibits Transforming Growth Factor-β-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

IL-10 通过 JNK 和 p38 途径抑制人肺成纤维细胞中转化生长因子-β 诱导的 I 型胶原蛋白 mRNA 表达

• 发表时间: 2005
• 期刊: EXCLI Journal 4
• 作者: Terasaki Y;Akuta T;Terasaki M;Sawa T;Mori T;Okamoto T;Ozaki M;Takeya M;Akaike T.;桑野和善;Inoue K
• 通讯作者: Inoue K

Alveolar macrophages and emphysema in surfactant protein-D-deficient mice.

表面活性蛋白 D 缺陷小鼠的肺泡巨噬细胞和肺气肿。

• 发表时间: 2006
• 期刊: Respirology 11 Suppl 1
• 作者: Komohara Y;Hirahara J;Horikawa T;Kawamura K;Kiyota E;Sakashita N;Araki N;Takeya M.;Yoshida M
• 通讯作者: Yoshida M

Anti-fibrotic effects of theophylline on lung fibroblasts.

• DOI: 10.1016/j.bbrc.2006.01.018
• 发表时间: 2006-03
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Y. Yano;Mitsuhiro Yoshida;S. Hoshino;Koji Inoue;H. Kida;M. Yanagita;T. Takimoto;H. Hirata;T. Kijima;T. Kumagai;T. Osaki;I. Tachibana;I. Kawase

Anti-fibrotic Effects of ONO-EF-345, a Specific Phosphodiesterase IV inhibitor, on Lung Fibroblasts

特异性磷酸二酯酶 IV 抑制剂 ONO-EF-345 对肺成纤维细胞的抗纤维化作用

• 发表时间: 2007
• 期刊: EXCLI Journal 6
• 作者: Fukuoka Y;et al.;Yanagita M
• 通讯作者: Yanagita M

The Extracellular Domain of p185(c-neu) Induces Density-Dependent Inhibition of Cell Growth in Malignant Mesothelioma Cells and Reduces Growth of Mesothelioma In Vivo.

p185(c-neu) 的胞外结构域可诱导恶性间皮瘤细胞中细胞生长的密度依赖性抑制，并减少体内间皮瘤的生长。

• 发表时间: 2006
• 期刊: DNA Cell Biol. 25(9)
• 作者: Yoneda T;et al.
• 通讯作者: et al.