WEKO3
アイテム
Visualization of Domain- and Concentration-Dependent Impact of Thrombomodulin on Differential Regulation of Coagulation and Fibrinolysis
http://hdl.handle.net/10271/0002000100
http://hdl.handle.net/10271/000200010034882892-dfb8-4d29-b1cb-24b51af3c267
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
DT_925ronbun.pdf (11.3 MB)
|
.png)
|
| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
|---|---|---|---|---|---|---|---|---|
| 公開日 | 2024-03-08 | |||||||
| タイトル | ||||||||
| タイトル | Visualization of Domain- and Concentration-Dependent Impact of Thrombomodulin on Differential Regulation of Coagulation and Fibrinolysis | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | fibrinolysis | |||||||
| キーワード | ||||||||
| 主題 | thrombomodulin | |||||||
| キーワード | ||||||||
| 主題 | anticoagulant | |||||||
| キーワード | ||||||||
| 主題 | platelets | |||||||
| キーワード | ||||||||
| 主題 | fluorescence | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | 凝固と線溶の異なる調節系におけるトロンボモジュリンのドメインならびに濃度依存性作用の可視化 | |||||||
| 著者 |
望月, 里依奈
× 望月, 里依奈
|
|||||||
| 書誌情報 |
en : Thrombosis and Haemostasis 巻 123, 号 1, p. 16-26, 発行日 2023-01 |
|||||||
| 出版者 | ||||||||
| 出版者 | Georg Thieme Verlag KG | |||||||
| 言語 | en | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | (c) 2022. Thieme. All rights reserved. | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Background Thrombomodulin (TM) functions as a dual modulator—anticoagulant and antifibrinolytic potential—by the thrombin-dependent activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI). Activated TAFI cleaves the C-terminal lysine of partially degraded fibrin and inhibits both plasminogen binding and its activation on the fibrin surface. We have reported previously that activated platelets initiate fibrin network formation and trigger fibrinolysis after the accumulation of tissue-type plasminogen activator and plasminogen. Objective To analyze the effects of domain-deletion variants of TM on coagulation and fibrinolysis at different concentrations. Methods Domain-deletion variants of TM, such as D123 (all extracellular regions), E3456 (minimum domains for thrombin-dependent activation of protein C and TAFI), and E456 (minimum domains for that of protein C but not TAFI), were used at 0.25 to 125 nM for turbidimetric assay to determine the clotting time and clot lysis time and to visualize fibrin network formation and lysis in platelet-containing plasma. Results and Conclusions A low concentration of either D123 or E3456, but not of E456, prolonged clot lysis time, and delayed the accumulation of fluorescence-labeled plasminogen at the activated platelets/dense fibrin area due to effective TAFI activation. Conversely, only the highest concentrations of all three TM variants delayed the clotting time, though fibrin network formation in the vicinity of activated platelets was almost intact. TAFI activation might be affected by attenuation in thrombin activity after the clot formation phase. These findings suggest that the spatiotemporal balance between the anticoagulant and antifibrinolytic potential of TM is controlled in domainand concentration-dependent manners. |
|||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2023-03-09 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第925号 | |||||||
| ISSN | ||||||||
| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 0340-6245 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 2567-689X | |||||||
| NII書誌ID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA00863137 | |||||||
| PubMed番号 | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 36307100 | |||||||
| 出版社DOI | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1055/s-0042-1757407 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
