2017 Fiscal Year Final Research Report
Roles of Notch signaling and hexosamine pathway on regulation of blood brain barrier
| Project/Area Number |
15K15064
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小川 光貴 名古屋大学, 医学系研究科, 助教 (70727429)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | Notch / O-GlcNAc / 血管integrity |
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| 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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| Free Research Field |
糖鎖生物学
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