| Project/Area Number |
26860208
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Niigata University |
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Principal Investigator |
Kato Taisuke 新潟大学, 脳研究所, 特別研究員 (30598496)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | TGFβ / small vessel disease / CARASIL / HTRA1 / smooth muscle cell / pericyte / TGFβシグナル / 脳小血管病 / 細胞外マトリクス / TGF-β / 血管平滑筋細胞 |
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| Outline of Final Research Achievements |
The purpose of this study is to clarify whether the excessive TGFβ signaling induces the pathology of cerebral small vessel diseases (CSVD). We found that transgenic mice that overproduce a TGFβ1 (TGFβ1 Tg) display structural alterations and loss of smooth muscle cells on the vessel walls resembling that of patients with CSVD. On the capillaries in parenchyma, decrease in pericyte coverage was seen in the brain of TGFβ1 Tg mice.
In addition, we found the accumulations of LTBP in cerebral arteries of mice deficient for HTRA1 (high temperature requirement A1) which is the causative gene for CARASIL, one of the inherited CSVD. LTBP covalently bind to TGFβs and regulate its signaling. These results not only elucidated the molecular mechanisms by which loss of HTRA1 function leads to enhancement of TGFβ signaling, but also demonstrated excessive TGFβ signaling results in the manifestation of CSVD pathology in vivo.
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