EVALUATING THE PATHOGENESIS AND DEVELOPMENT OF NOVEL THERAPIES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE USING GENE-ENGINEERED MICE

使用基因工程小鼠评估慢性阻塞性肺疾病的发病机制和新疗法的开发

• 批准号: 21590133
• 负责人: TAGUCHI Osamu
• 金额: $ 2.91万
• 依托单位: Mie 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590133/
• 关键词: 閉塞性肺疾患; 煙草; 高齢者; 炎症性サイトカイン; プロテアーゼ; 肺胞破壊; 炎症性細胞; 肺気腫; 樹状細胞; マトリックスメタロプロテーゼ; サイトカイン; 活性かプロテインC; 気管支炎; 慢性閉塞性肺疾患; タバコ; 血管内皮細胞傷害; 凝固系因子; 肺胞上皮細胞傷害; 活性化プロテインC; 肺傷害; 凝固系; トロンビン受容体; T細胞; 慢性気管支炎; トロンビン

In the present investigation, activated protein C(APC) and thrombomodulin(TM) showed significant suppressive activity on the expression of cytokines and proteases from dendritic cells, alveolar epithelial cells and inflammatory cells. In addition, we succeeded in the design and development of human transforming growth factor-β1(TGFβ1) and human metalloproteinase-2(MMP-2) transgenic mice, and demonstrated the involvement of both TGFβ1 and MMP-2 in the pathogenesis of COPD. Further, we are currently carrying out several in vivo studies to demonstrate the effect of APC and TM on the pulmonary lesions induced in both TGFβ1 and MMP-2 transgenic mice.

在介绍研究中，激活的蛋白C（APC）和血小板蛋白（TM）在树突状细胞，肺泡上皮细胞和炎性细胞的细胞因子和蛋白质表达上表现出显着的抑制活性。此外，我们在人类转化生长因子-β1（TGFβ1）和人金属蛋白酶-2（MMP-2）转基因小鼠的设计和开发中取得了成功，并证明了TGFβ1和MMP-2在COPD发病机理中的参与。此外，我们目前正在进行几项体内研究，以证明APC和TM对TGFβ1和MMP-2转基因小鼠诱导的肺水平的影响。

项目成果

Direct effects of protein S in ameliorating acute lung injury

• DOI: 10.1111/j.1538-7836.2009.03642.x
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
• 影响因子: 10.4
• 作者: Takagi, T.;Taguchi, O.;Gabazza, E. C.
• 通讯作者: Gabazza, E. C.

Role of the complement system in exacerbation of acute lung injury in Thrombin-Activatable fibrinolysis inhibitor-deficient mice

补体系统在凝血酶激活纤溶抑制剂缺陷小鼠急性肺损伤恶化中的作用

• 发表时间: 2011
• 作者: 内藤雅大,田口修,高木健裕,戸田雅昭,小林哲,三宅泰士;Boveda-Ruiz D;D' Alessandro-Gabazza;C;Gabazza EC
• 通讯作者: Gabazza EC

The coagulation and protein C pathways in patients with sleep apnea

睡眠呼吸暂停患者的凝血和蛋白 C 通路

• 发表时间: 2009
• 期刊: Lung
• 影响因子: 5
• 作者: Takagi T;Morser J;Gabazza EC;Qin L;Fujiwara A;Naito M;Yamaguchi A;Kobayashi T;D' Alessandro-Gabazza CN;Boveda Ruiz D;Gil Bernabe P;Iwasaki Y;Takei Y;Taguchi O
• 通讯作者: Taguchi O

Lung Radiofrequency Ablation for the Treatment of Unresectable Recurrent Non-Small-Cell Lung Cancer After Surgical Intervention

• DOI: 10.1007/s00270-011-0220-0
• 发表时间: 2012-06
• 期刊: CardioVascular and Interventional Radiology
• 影响因子: 2.9
• 作者: H. Kodama;K. Yamakado;H. Takaki;M. Kashima;J. Uraki;A. Nakatsuka;M. Takao;O. Taguchi;Tomomi Yamada;K. Takeda

Thrombomodulin modulates maturation and antigen presentation of murine dendritic cells in vitro

血栓调节蛋白在体外调节鼠树突状细胞的成熟和抗原呈递

• 发表时间: 2010
• 作者: Toda M;Takagi T;Taguchi O;Boveda-Ruiz D;Gil-Bernabe P;D' Alessandro-Gabazza CN;Miyake Y;Yasukawa A;Morser J;Gabazza EC.
• 通讯作者: Gabazza EC.