Elucidation of functional involvement of RGM, an inhibitory factor for neuronal regeneration, and development of RGM-targeted therapy in critical illness.
| Project/Area Number |
18H02903
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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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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
Matsumoto Naoya 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (50359808)
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| Co-Investigator(Kenkyū-buntansha) |
田島 吾郎 長崎大学, 病院(医学系), 助教 (00437427)
田崎 修 長崎大学, 病院(医学系), 教授 (90346221)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | RGMa / 頭部外傷 / neogenin / 再生医療 / ミクログリア / 脳損傷 / 炎症 / マウス / Neogenin / 次世代シークエンサー / バイオインフォマティクス / マクロファージ / RGM / 神経再生治療 / 神経再生 / サイトカイン / RT-PCR / 敗血症 / 免疫応答異常 / 免疫組織化学 |
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| Outline of Final Research Achievements |
RGMa is a key protein to regulate nerve regeneration negatively. Its inhibition enhances axonal growth and promotes functional recovery in spinal cord injury. The purpose of this study is to clarify traumatic brain injury-responsive RGMa expression in a murine model. mRNA expressions of inflammatory cytokines were remarkably increased at day 1 and gradually decreased over time. mRNA expressions of RGMa and its receptor, Neogenin were significantly suppressed in the damaged cortex until day 3. RGMa expression was suppressed most at day 1 and up-regulated over time. In the acute phase, RGMa and Neogenin were significantly decreased under inflammatory milieu. Contrary to the subsequent inflammatory remission, RGMa expression recovered rapidly to normal level. Intrinsic regenerative response to acute brain injury might be hampered by following up-regulation of RGMa, hinting the possibility of functional RGMa inhibition as a new effective maneuver against traumatic brain injury.
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| Academic Significance and Societal Importance of the Research Achievements |
頭部外傷によって引き起こされる脳損傷は恒久的な後遺症を残し，患者や家族の心理的，経済的負担は甚大である。高齢化社会を迎えた今，頭部外傷患者が増加の一途をたどっており社会的な問題となっている。哺乳類の中枢神経は一旦損傷すると再生しない。幹細胞移植を代表とする再生医療が華やいでいるが，期待したレベルまでの成果が得られていない。本研究により，神経再生阻害因子であるRGMaが脳損傷に応答してダイナミックな発現変化を示し，超急性期にRGMa機能を抑制することで神経再生・保護が促進される可能性が示唆された。すでに脊髄損傷に対して臨床治験が進められている抗RGMa抗体治療の頭部外傷への拡大応用が期待される。
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Report
(5 results)
Research Products
(3 results)
