| Project/Area Number |
17K01945
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Discontinued (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | cellular Factor XIII-A / heat shock factor 1 / optic nerve injury / zebrafish / retina / regeneration / activation peptides / short type cFXIII-A / HSF-1 / CNS regeneration / 急性相反応物質 / 創傷治癒 / Factor XIII-A / transglutaminase / optic nerve / wound healing / heat shock factor / optioc nerve |
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| Outline of Final Research Achievements |
Cellular Factor XIII (cFXIII), which is distributed in various tissues and cells, usually exists as an inactive type. Here, we investigated the molecular mechanism of cFXIII gene activation using genetic information from the A-subunit of cFXIII (cFXIII-A). cFXIII-A mRNA, lack of "activation peptides" cording region, is rapidly upregulated in the zebrafish retina after optic nerve injury. Chromatin immunoprecipitation provides direct evidence of enrichment of cFXIII-A genomic DNA bound with heat shock factor 1 (HSF-1), which is immediately upregulated in damaged retina. These findings indicate that rapid HSF-1 binding to the cFXIII-A gene results in an active form of cFXIII-A protein in the zebrafish retina after optic nerve injury without thrombin.
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| Academic Significance and Societal Importance of the Research Achievements |
血液凝固因子のFactor XIIII-Aについては、トロンビンが活性化されることによって"Activation peptides"が切断され、活性化タイプのFXIII-Aに変化することが知られている。ところが、組織中や細胞に存在するcellular FXIII-A (cFXIII-A) の活性化機構については、十分な知見が得られていなかった。
今回のゼブラフィッシュの視神経損傷モデルを使用することにより、まず、Heat shock factor 1が視神経損傷後のごく初期の段階で発現増加し、この関与によって、直接、活性化タイプのcFXIII-Aが発現するという、新たな活性化機構が解明された。
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