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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）是过量的纤维结缔组织形成的过程，其特征在于纤维状胶原的积聚。四跨膜蛋白是整联蛋白的重要组成部分，它促进多种分子复合物的形成并调节细胞功能。我们先前报道了在自发形成COPD样表型的小鼠中四跨膜蛋白CD 9和CD 81的双缺失。来自DNA微阵列的基因功能分析意外地揭示了“结缔组织发育和功能”在CD 151 KO肺中排名靠前。值得注意的是，随着年龄的增长，CD 151 KO小鼠自发地发生肺纤维化。结论：CD 151基因敲除小鼠肺组织中p-Smad 2表达水平在全肺和肺上皮中均升高。事实上，肺泡上皮细胞中CD 151的缺失导致基质胶上的p-Smad 2活性增加和间充质样变化。有趣的是，与健康对照相比，IPF患者上皮细胞中CD 151的表达下调。鉴于CD 151通过维持上皮完整性在预防纤维化中起着关键作用，CD 151可能是PF的新靶点。

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