Analysis of pleiotropic property of thrombomodulin and development of therapeutic strategy using thrombomodulin in transplantation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Aichi Medical University (2015); Nagoya University (2013-2014)
• Principal Investigator: MIWA YUKO 愛知医科大学, 医学部, 寄附講座 助教 (90572941)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI TAKAAKI 愛知医科大学, 医学部 外科学講座(腎移植外科), 教授 (70314010) ; IWASAKI KENTA 愛知医科大学, 医学部 腎疾患・移植免疫学寄附講座, 准教授 (10508881)
• Co-Investigator(Renkei-kenkyūsha): ONISHI AKIRA 日本大学, 生物資源科学部, 教授 (30414890)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 移植・再生医療 / 凝固系制御 / 異種移植

Outline of Final Research Achievements

Thrombomodulin (TM) is a vascular endothelial cell receptor that functions as a cofactor for activated protein C (APC). From the viewpoint of coagulation control using TM in transplantation, two strategy including (i) administration of recombinant soluble thrombomodulin (S-hTM), which has been approved for the treatment of sepsis-induced DIC, and (ii) upregulation of membrane-bound TM (MB-hTM) expression in endothelial cells would be proposed. As a result, S-hTM had more potent capacity of APC production and inhibitory effect on thrombin generation than MB-hTM. In contrast, MB-hTM suppressed the expression of inflammatory factor in endothelial cells. It was speculated that S-hTM treatment would be of assistance during high-risk periods for excessive thrombin formation (e.g., ischemia reperfusion injury or severe　infection/rejection). Considering the properties of MB-hTM exhibiting anti-inflammatory function, might be required to long-term stabilization of graft endothelial cells.

Free Research Field

移植免疫学