Significance of transcriptional regulation in postnatal angiogenesis

转录调控在出生后血管生成中的意义

• 批准号: 21790742
• 负责人: HAYASHI Hisaki
• 金额: $ 2.75万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790742/
• 关键词: 血管新生; 転写因子; シグナル伝達; 虚血; 血管内皮細胞; 下肢動脈結紮モデル; 転写調節因子

Cerebral and myocardial infarction and cancer are leading causes of mortality in developed countries, and therefore it is of clinical importance to study the mechanisms of pathological angiogenesis, especially the signaling pathways regulating vascular formation, in those diseases. Hairy-related transcription factor 1 (Hrt1) and Hrt2 are basic helix-loop-helix proteins enriched in the cardiovascular system, and their expression is directly up-regulated by the Notch signaling activation. So far, importance of Hrt molecules in developmental angiogenesis was reported, however, their significance in postnatal physiology, especially in angiogenesis, remained unclear. In this study, we demonstrated that Hrt1 mRNA expression was significantly induced upon hindlimb ischemia by the femoral artery occlusion. Interestingly, blood flow recovery after the surgery was markedly attenuated in Hrt1 KO mice, suggesting that Hrt1 is involved in postnatal angiogenesis. The roles of Hrt2 and molecular mechanisms of their function in postnatal angiogenesis are currently under extensive investigation.

大脑和心肌梗死和癌症是发达国家死亡率的主要原因，因此研究病理血管生成的机制，尤其是调节血管形成的信号传导途径，在这些疾病中具有临床重要性。与毛状相关的转录因子1（HRT1）和HRT2是富含心血管系统的基本螺旋 - 环螺旋螺旋蛋白，它们的表达直接被Notch信号激活而上调。到目前为止，据报道，HRT分子在发育血管生成中的重要性，但是它们在产后生理学中的重要性，尤其是在血管生成中，尚不清楚。在这项研究中，我们证明了股动脉闭塞在后肢缺血时显着诱导HRT1 mRNA表达。有趣的是，手术后的血流恢复在HRT1 KO小鼠中显着减弱，这表明HRT1参与了产后血管生成。目前，HRT2的功能在产后血管生成中的作用和分子机制目前正在广泛研究中。

项目成果

Significance of Hrt family of transcription factors in postnatal angiogenesis

Hrt转录因子家族在出生后血管生成中的意义

• 发表时间: 2011
• 作者: Hisaki Hayashi