Roles of Notch signaling and hexosamine pathway on regulation of blood brain barrier
Project/Area Number |
15K15064
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
General medical chemistry
|
Research Institution | Nagoya University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
小川 光貴 名古屋大学, 医学系研究科, 助教 (70727429)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | Notch / O-GlcNAc / 血管integrity / 血液脳関門 / NOTCH / 糖鎖 / EOGT / BBB / BRB |
Outline of Final Research Achievements |
Notch receptors are modified with unique post-translational modifications on epidermal growth (EGF)-like repeats. Previous studies elucidated the presence of O-GlcNAc modification and O-GlcNAc transferase, EOGT. O-GlcNAc modification by EOGT regulates DLL4-mediated Notch1 activation. In this study, we investigated roles of O-GlcNAc-mediated Notch regulation on integrity of blood vessels, which is pivotal for blood brain barrier. In Eogt-deficient mice, extravasation of biotin derivatives and deposition of fibrinogen were detected. Similar phenotype was observed in endothelial deletion of EOGT. In addition to N-cadherin, expression of components of tight junction were decreased, suggesting that EOGT-dependent Notch signaling represents a novel mechanism for regulation of blood vessels integrity.
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Report
(4 results)
Research Products
(16 results)