Development of a novel treatment strategy to protect vascular endothelial cells with TM mutant

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02844
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Ikezoe Takayuki 福島県立医科大学, 医学部, 教授 (80294833)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: トロンボモジュリン

Outline of Final Research Achievements

Thrombomodulin is a glycoprotein comprising several distinct structures and is mainly expressed on endothelial cell surfaces. TM negatively regulates the coagulation system and human recombinant TM consisting of an extracellular domain of TM is approved in Japan for treatment of patients with disseminated intravascular coagulation. We had recognized that rTM possesses vascular endothelial cytoprotective effects and initiated the experiments to explore the molecular mechanism by which rTM exerts cytoprotective effects and attempted to identify the minimal region of TM that produces cytoprotective function. We found that 19 amino acid structure within epidermal growth factor-like region of TM possesses angiogenic and cytoprotective function.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

造血細胞移植は白血病をはじめ難治性血液がんに根治をもたらし得る画期的な治療法であるが、血管内皮細胞障害に起因する血栓性微小血管症や肝類洞閉塞症候群などによる非再発死亡が多く、その治療成績は未だ満足できるものではない。今回我々が見出した19アミノ酸を使用することで血管内皮細胞障害に起因する移植関連合併症を予防でき、移植成績の向上が期待できる。