Mechanisms of hypoxia-induced transformation in endothelial cells

缺氧诱导内皮细胞转化的机制

• 批准号: 21590335
• 负责人: TOMITA Shuhei
• 金额: $ 3万
• 依托单位: The University of Tokushima
• 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-21590335/
• 关键词: 分子病態学; 低酸素; 血管内皮細胞; 低酸素応答; 肺高血圧症; 転写因子; HIF; 微小環境; 酸化ストレス; 活性酸素

MCT-induced pulmonary arteries demonstrated binding of pimonidazole, a hypoxia detection agent that binds to regions of hypoxia in the region around vascular walls including lung epithelial cells. Indices of the PAH were significantly alleviated in the Hif-1β+/-mice compared to the control as the following data showed ; the weight ratio of right ventricular to left ventricular with septum was significantly decreased ; the number of pulmonary arteries was significantly increased ; indices of the medial thickness was significantly decreased. The number of musculized pulmonary arteries in MCT-treated Hif-1β+/-mice was significantly decreased compared to that of the control mice. In addition, interestingly, the PAH in wild type mice was ameliorated by administration of bosentan, an endothelin receptor blocker, to the same level of that in Hif-1β+/-mice. These results indicate that the development of MCT-induced PAH was mediated by HIF-1βin endothelial cells.

MCT诱导的肺动脉表现出pimonidazole的结合，Pimonidazole是一种缺氧检测剂，与包括肺上皮细胞在内的血管壁周围的低氧区域结合。如以下数据所示，与对照相比，在HIF-1β+/-小鼠中，PAH的指标显着缓解。右心室与隔膜的左心室的重量比显着增加。肺动脉的数量显着增加；介质厚度的指标得到了显着改善。与对照小鼠相比，MCT治疗的HIF-1β+/-小鼠中肌肉肺动脉的数量显着减少。此外，有趣的是，野生型小鼠中的PAH通过在HIF-1β+/-小鼠中的内皮素接收器阻断剂波森坦（Bosentan）进行改善。这些结果表明，MCT诱导的PAH的发展是由HIF-1βIN内皮细胞介导的。

项目成果

Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells

• DOI: 10.1038/hr.2010.63
• 发表时间: 2010-07-01
• 期刊: HYPERTENSION RESEARCH
• 影响因子: 5.4
• 作者: Tajima, Soichiro;Tsuchiya, Koichiro;Tamaki, Toshiaki
• 通讯作者: Tamaki, Toshiaki

Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells

• DOI: 10.2152/jmi.58.118
• 发表时间: 2011-02-01
• 期刊: JOURNAL OF MEDICAL INVESTIGATION
• 影响因子: 0.7
• 作者: Fukuhara, Yayoi;Tsuchiya, Koichiro;Tamaki, Toshiaki
• 通讯作者: Tamaki, Toshiaki

Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner.

• DOI: 10.1093/ndt/gfp520
• 发表时间: 2010-02
• 期刊: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
• 作者: K. Ishizawa;Y. Izawa-Ishizawa;Narantungalag Dorjsuren;Erika Miki;Y. Kihira;Yasumasa Ikeda;S. Hamano;K. Kawazoe;K. Minakuchi;S. Tomita;K. Tsuchiya;T. Tamaki

Nitroso-Nifedipine is A New Class Drug to Protect Endotherial Function for Overcoming Organ Damage

亚硝基硝苯地平是一种保护内皮功能、克服器官损伤的新型药物

• 发表时间: 2010
• 作者: Ishizawa K;Imanishi M;Horinouchi Y;Fukuhara Y;Izawa-Ishizawa Y;Ikeda Y;Kihira Y;Tomita S;Tsuchiya K;Tamaki T
• 通讯作者: Tamaki T

Amelioration of acute tubular necrosis in ischemic acute renal failure was impaired in mice lacking hypoxia inducible factor-1 gene

缺乏缺氧诱导因子-1基因的小鼠对缺血性急性肾功能衰竭急性肾小管坏死的改善作用受损

• 发表时间: 2010
• 作者: Tamaki T;Yamaguchi K;Kihira Y;Ikeda Y;Ishizawa K;Tsuchiya K;Tomita S.
• 通讯作者: Tomita S.