2022 Fiscal Year Final Research Report
Elucidation of Individual Variance Factors in the Clinical Effectiveness of Thrombomodulin-alpha and Establishment of Novel Therapeutic Strategies for DIC
Project/Area Number |
19K16427
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Suzuka University of Medical Science |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | トロンボモデュリンアルファ / DIC / 敗血症 |
Outline of Final Research Achievements |
This study elucidated the interactions and functions of thrombomodulin alpha (TMα) and suggested potential new therapeutic strategies. TMα was found to interact directly with PLA2G2A, and it was suggested that its anti-inflammatory effect might be exerted by competitively affecting the interaction between ITGαVβ3 and PLA2G2A. TMα also interacts with the S100A8/S100A9 heterodimer, although its functional implications remain unclear. On the other hand, while TMα is known to interact with LPS, it does not inhibit the interaction with LBP or sCD14. It has been suggested that the anti-inflammatory effect of LPS may be due to inhibition of LPS recruitment to TLR4 by sCD14. These findings may contribute to the development of new therapies for DIC.
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Free Research Field |
臨床薬学
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Academic Significance and Societal Importance of the Research Achievements |
敗血症による播種性凝固血管内症候群(DIC)は死亡率が高い。ヒトトロンボモジュリン(TM)の遺伝子組み換え製剤であるTMαは、DICに対して唯一臨床効果が認められている薬物であるが、その詳細な機序は解明されてない。また、TMαの臨床効果には個体差がみられ、臨床効果を最大に発揮するために、作用機序の全貌および個体差要因を解明することが急務となっている。本研究は、新たなTMαとの相互作用分子とその機能を発見した。本研究の成果は、ヒトTMの生物学的機能の解明に加え、DICの重症化に関連する因子やDICの新規治療戦略開発の可能性に繋がると考えられた。
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