Activation of Factor XIII-A in the acute phase of post injury and its involvement in wound healing

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K01945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Kanazawa University
• Principal Investigator: Sugitani Kayo 金沢大学, 保健学系, 助教 (20162258)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: cellular Factor XIII-A / heat shock factor 1 / optic nerve injury / zebrafish / retina / regeneration / activation peptides / short type cFXIII-A

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.

Free Research Field

神経化学

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。