Functional analysis of tetraspanins(CD9, CD151) in lung fibrosis

四跨膜蛋白(CD9、CD151)在肺纤维化中的功能分析

基本信息

批准号：
21590992
负责人：
TAKEDA Yoshito
金额：
$ 2.83万
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：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

Pulmonary fibrosis(PF) is the process whereby excess fibrous connective tissue forms and characterized by the accumulation of fibrillar collagen. Tetraspanins, key partners of integrins, facilitate the formation of multiple molecular complexes and regulate cell function. We previously reported double deletion of tetraspanin CD9 and CD81 in mice spontaneously developed COPD-like phenotype. The gene functions analyses from DNA Microarray unexpectedly revealed that' connective tissue development and function' were ranked high in CD151 KO lungs. Notably, CD151 KO mice spontaneously developed lung fibrosis with age. Consistently, the level of p-Smad2 in the CD151 KO mice was augmented in the whole lung and in the epithelium. Indeed, deletion of CD151 in alveolar epithelial cells leads to increased p-Smad2 activity on Matrigel, and mesenchymal-like changes. Of interest, expression of CD151 in epithelial cells from IPF patients was downregulated compared with that of healthy controls. Given that CD151 plays a pivotal role to prevent fibrosis through maintaining epithelial integrity, CD151 could be a novel target for PF.

肺纤维化（PF）是多余的纤维结缔组织形成的过程，其特征是原纤维胶原蛋白的积累。整联蛋白的关键伴侣四叠素蛋白促进了多个分子复合物的形成并调节细胞功能。我们先前报道了小鼠自发发展的COPD样表型的四跨蛋白CD9和CD81的双重缺失。来自DNA微阵列的基因功能分析出乎意料地表明，“结缔组织的发育和功能”在CD151 KO肺中排名很高。值得注意的是，CD151 KO小鼠随着年龄的增长而自发发展了肺纤维化。一致地，在整个肺和上皮中，CD151 KO小鼠中P-SMAD2的水平得到了增强。实际上，肺泡上皮细胞中CD151的缺失会导致p-SMAD2在母质上的活性增加，并类似间质的变化。有趣的是，与健康对照组相比，IPF患者的上皮细胞中CD151的表达被下调。鉴于CD151起着通过维持上皮完整性来防止纤维化的关键作用，因此CD151可能是PF的新目标。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

4-Hydroxy-2-nonenal induces chronic obstructive pulmonary disease-like histopathologic changes in mice

4-Hydroxy-2-nonenal 诱导小鼠慢性阻塞性肺病样组织病理学变化

DOI：
发表时间：
2012
期刊：
Biochem Biophys Res Commun
影响因子：
0
作者：
Takimoto T;Yoshida M;Hirata H;Kashiwa Y;Takeda Y;Goya S;Kijima T;Kumagai T;Tachibana I;Kawase I.
通讯作者：
Kawase I.

Cell Surface Tetraspanin CD9 Mediates Chemoresistance in Small Cell Lung Cancer