Exploration of a novel blood-coagulation cascade in vertebrate

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 40040:Aquatic life science-related
• Research Institution: Kitasato University
• Principal Investigator: Tsutsui Shigeyuki 北里大学, 海洋生命科学部, 准教授 (20406911)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: レクチン / 血液凝固 / 軟骨魚類 / プロトロンビン

Outline of Final Research Achievements

Heterodontus japonicus C-type lectin (HjCL), which was isolated from bullhead shark skin,is known to show procoagulant activity. However, how HjCL propagates the blood coagulation pathway has been in black box. In this study, we searched for the target factor of HjCL in the shark plasma and revealed the complete picture of the novel blood coagulation cascade.
Addition of HjCL to the shark plasma converted a 120-kDa protein to multiple fragments. Internal amino acid sequences of 120-kDa protein determined with de novo sequencing were matched to the amino acid sequence of the shark prothrombin (ProT). Moreover, HjCL induced the cleavage of the shark ProT purified form plasma, suggesting that HjCL directly affects on the zymogen.It was also revealed that HjCL generates the active enzyme thrombin from ProT. Finally, the fibrin-gel formation was detected from the mixture of HjCL, ProT and fibrinogen. Taken together, it is concluded that HjCL acts as a trigger of a novel coagulation cascade.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ネコザメの皮膚から単離したC-typeレクチンはネコザメ血漿中のプロトロンビンの分解を誘導した。また、この分解産物はヒトフィブリノーゲンをゲル化した。以上により、レクチンがプロトロンビンに直接的に作用する新奇血液凝固カスケードの全貌が明らかになったと共に、ヒトに対する医療分野にも応用できる可能性が示唆された。