Investigation of role for MafB in the pathogenesis of chronic obstructive pulmonary disease using MafB gene targeted mice

使用 MafB 基因靶向小鼠研究 MafB 在慢性阻塞性肺疾病发病机制中的作用

• 批准号: 23390220
• 负责人: SHIBATA Yoko
• 金额: $ 12.06万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390220/
• 关键词: COPD; MafB; マクロファージ; 喫煙; 転写因子; マトリックスメタロプロテアーゼ; エラスターゼ肺気腫

Role of MafB in the pathogenesis of chronic obstructive pulmonary disease (COPD) was investigated using macrophage scavenger receptor promoter dominant negative-MafB transgenic (MSR-DN-MafB TG) mice. Mean linear intercept after intratracheal administration of elastase was significantly reduced in TG mice compared to the wild type mice (WT). In TG mice, number of alveolar macrophages (AMs) with projected pseudopods was significantly reduced. In addition, number of F4/80 intermediately positive and CD11b weakly or intermediately positive AMs, considerable cell subsets of matured AMs, decreased in BAL cells of DN-MafB Tg mice. Furthermore, the expression of MMP-9 and -12 was suppressed significantly in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema pathogenesis through altering the maturation of macrophages and the expression of MMPs.

使用巨噬细胞清道夫受体启动子显性失活的 MafB 转基因 (MSR-DN-MafB TG) 小鼠研究了 MafB 在慢性阻塞性肺疾病 (COPD) 发病机制中的作用。与野生型小鼠 (WT) 相比，TG 小鼠气管内施用弹性蛋白酶后的平均线性截距显着降低。在 TG 小鼠中，具有投射伪足的肺泡巨噬细胞 (AM) 数量显着减少。此外，DN-MafB Tg 小鼠的 BAL 细胞中 F4/80 中度阳性和 CD11b 弱或中度阳性 AM（成熟 AM 的相当大的细胞亚群）的数量减少。此外，DN-MafB Tg 小鼠的 BAL 细胞中 MMP-9 和 -12 的表达显着受到抑制。由于MMPs会加剧肺气肿，MafB可能通过改变巨噬细胞的成熟和MMPs的表达参与肺气肿的发病机制。

项目成果

Dominant negative(DN)MafBトランスジェニックマウスを用いた急性肺障害モデルの検討

使用显性阴性 (DN) MafB 转基因小鼠检查急性肺损伤模型

• 发表时间: 2012
• 作者: 會田康子;山内啓子;他
• 通讯作者: 他

Impairment of pulmonary function is an independent risk factor for atrial fibrillation: the Takahata study.

• DOI: 10.7150/ijms.8.514
• 发表时间: 2011
• 期刊: International journal of medical sciences
• 影响因子: 3.6
• 作者: Shibata Y;Watanabe T;Osaka D;Abe S;Inoue S;Tokairin Y;Igarashi A;Yamauchi K;Kimura T;Kishi H;Aida Y;Nunomiya K;Nemoto T;Sato M;Konta T;Kawata S;Kato T;Kayama T;Kubota I
• 通讯作者: Kubota I

Relationships between values of antibodies to several connective tissue disease autoantigens and pulmonary function in a Japanese general population: the Takahata study.

• DOI: 10.1371/journal.pone.0081678
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Nakano H;Shibata Y;Inoue S;Igarashi A;Yamauchi K;Abe S;Sato M;Aida Y;Nunomiya K;Kimura T;Nemoto T;Watanabe T;Konta T;Ueno Y;Kato T;Kayama T;Kubota I
• 通讯作者: Kubota I

MafB Suppresses Acute Inflammatory Responses In Lipopolysaccharide -Stimulated Lung Injury In Mice

MafB 抑制脂多糖刺激的小鼠肺损伤的急性炎症反应

• 发表时间: 2012
• 作者: Aida Y;Yamauchi K;et al
• 通讯作者: et al

Two cases of bronchiolitis obliterans organizing pneumonia syndrome after postoperative irradiation for breast cancer

乳腺癌术后照射后闭塞性细支气管炎伴肺炎综合征二例

• 发表时间: 2011
• 期刊: EXCLI J
• 影响因子: 4.6
• 作者: Inoue S;Shibata Y;et al
• 通讯作者: et al