The role of Notch3 receptor on destruction of the vascular smooth muscle cells in the brain arteries.

Notch3 受体对脑动脉血管平滑肌细胞破坏的作用。

• 批准号: 15590920
• 负责人: TAKAHASHI Keikichi
• 金额: $ 2.24万
• 依托单位: National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology (2004)National Center of Neurology and Psychiatry (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590920/
• 关键词: Notch3; CADASIL; Vascular smooth muscle cells; Vascular dementia; Signal transduction; Jagged; Microarray analysis; Calcium channel; 血管性痴呆; シグナル受容体; 血管平滑筋; 白質脳症

Mutations in the Notch3 receptor are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL). Brains of patients affected by CADASIL show degeneration of vascular smooth muscle cells(SMC) and the abnormal accumulation of the extracellular domain(ECD) of Notch3. However, the mechanisms underlying pathological alterations in CADASIL are unclear.In the present study, we determined specific genes which were regulated in vascular smooth muscle cells by Notch3. By the DNA array analysis, we found three genes. TARA-like protein gene and calcium channel were induced by the treatment of ligands, while DUSP23 were decreased. These genes may relate to proliferation and differentiation of vascular smooth muscle cells.

Notch3受体突变与常染色体显性遗传性脑动脉病伴皮质下梗塞和白质脑病(CADASIL)相关。CADASIL患者的大脑表现为血管平滑肌细胞(SMC)变性和Notch3胞外区(ECD)的异常积聚。然而，CADASIL病理改变的机制尚不清楚。在本研究中，我们确定了Notch3调控血管平滑肌细胞的特定基因。通过DNA阵列分析，我们发现了三个基因。配体处理诱导了类Tara蛋白基因和钙通道的表达，而DUSP23表达下降。这些基因可能与血管平滑肌细胞的增殖和分化有关。

项目成果

Notchシグナル異常と血管障害

Notch信号异常和血管疾病

• 发表时间: 2005
• 期刊: Molecular Medicine 42(発表予定)
• 作者: 吉崎嘉一;高橋慶吉
• 通讯作者: 高橋慶吉

Notch signaling and cerebral arteriopathy

Notch信号传导与脑动脉病

• 发表时间: 2005
• 期刊: Molecular Medicine 42
• 作者: Kaichi Yoshizaki;Keikichi Takahashi
• 通讯作者: Keikichi Takahashi

Santa Y et al.: "Genetic, clinical and pathological studies of CADASIL in Japan : a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis."J.Neurol.Sci.. 212. 79-84 (2003)

Santa Y 等人：“日本 CADASIL 的遗传学、临床和病理学研究：Notch3 突变的部分贡献以及平滑肌细胞变性对发病机制的影响。”J.Neurol.Sci.. 212. 79-84 (2003