Study on a microglial phenotypic switch with a focus on proteolytic response
| Project/Area Number |
15H05015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
武 洲 九州大学, 歯学研究院, 准教授 (10420598)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | ミクログリア / カテプシン / プロテアーゼ反応 / 分子スイッチ / カテプシンB / M1/M2極性転換 / 炎症疼痛 / 疼痛炎症 |
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| Outline of Final Research Achievements |
The mean mRNA levels of both M1 and M2 markers in microglia acutely isolated from the hippocampus of wild-type mice were gradually and significantly increased after brain injury. In contrast, the mean mRNA levels of M1 markers in microglia acutely isolated from the hippocampus of cathepsin B-deficient mice showed no significant change after brain injury. The mean mRNA levels of the M2 markers increased rather rapidly to reach a peak after brain injury and then returned to the control level. Furthermore, cathepsin E-dependent proteasomal system is involved in an early activation of NF-kB in microglia after brain injury. Autophagy caused a delayed but long-lasting activation of NF-kB through cathepsin B-mediated autophagy machinery in microglia. Therefore, a proteolytic relay through modulator actions of cathepsins E and B could work as a phenotypic switch in microglia along the M1-M2 phenotypic continuum through the dynamics of NF-kB activity.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] BK channels in microglia are required for2016
Author(s)
Yoshinori Hayashi, Saori Morinaga, Jing Zhang, Yasushi Satoh, Andrea Meredith, Takahiro Nakata, Zhou Wu, Shinichi Kohsaka, Kazuhide Inoue, Hiroshi Nakanishi
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Journal Title
Nature communications
Volume: 7
Issue: 1
Pages: 11697-11697
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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