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 诱导的肺动脉显示出哌莫硝唑的结合，哌莫硝唑是一种缺氧检测剂，可与血管壁周围区域（包括肺上皮细胞）的缺氧区域结合。与对照相比，Hif-1β+/-小鼠的PAH指数显着减轻，如下数据所示；右心室与左心室带间隔重量比显着降低；肺动脉数量显着增加；内侧厚度指数显着下降。与对照小鼠相比，MCT 治疗的 Hif-1β+/- 小鼠的肌肉化肺动脉数量显着减少。此外，有趣的是，通过给予内皮素受体阻滞剂波生坦，野生型小鼠的 PAH 得到改善，达到与 Hif-1β+/- 小鼠相同的水平。这些结果表明，MCT 诱导的 PAH 的发生是由内皮细胞中的 HIF-1β 介导的。

项目成果

Adiponectin inhibits insulin-like growth factor-1-induced cell migration via the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells.

脂联素通过抑制细胞外信号调节激酶 1/2 的激活来抑制胰岛素样生长因子 1 诱导的细胞迁移，但不抑制血管平滑肌细胞中的 Akt。

• 发表时间: 2009
• 期刊: Hypertens Res 32
• 作者: Motobayashi Y;et al.
• 通讯作者: et al.

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Pathophysiological Response to Hypoxia - From the Molecular Mechanisms of Malady to Drug Discovery:Inflammatory Responses of Hypoxia-Inducible Factor 1.ALPHA. (HIF-1.ALPHA.) in T Cells Observed in Development of Vascular Remodeling

对缺氧的病理生理反应 - 从疾病的分子机制到药物发现：缺氧诱导因子 1.ALPHA 的炎症反应。

• DOI: 10.1254/jphs.10r22fm
• 发表时间: 2011
• 期刊: Journal of Pharmacological Sciences
• 影响因子: 3.5
• 作者: Tomita S;et al
• 通讯作者: et al

Gene expression profile of third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development.

第三咽袋的基因表达谱揭示了间充质 MafB 在胚胎胸腺发育中的作用。

• 发表时间: 2009
• 期刊: Blood (In press)
• 作者: Sultana DA;et.al
• 通讯作者: et.al

Hypoxia-inducible factor-1a has a key role in hypoxic precon ditioning.

缺氧诱导因子1a在缺氧预适应中发挥着关键作用。

• 发表时间: 2009
• 期刊: J Clin Neurosci 16
• 作者: Taie S;et al.
• 通讯作者: et al.