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The lectin‐like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice
Author(s) -
Kawasoe Junya,
Uchida Yoichiro,
Miyauchi Tomoyuki,
Kadono Kentaro,
Hirao Hirofumi,
Saga Kenichi,
Watanabe Takeshi,
Ueda Shugo,
Terajima Hiroaki,
Uemoto Shinji
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16269
Subject(s) - medicine , thrombomodulin , ischemia , reperfusion injury , liver transplantation , disseminated intravascular coagulation , coagulopathy , anticoagulant , pharmacology , transplantation , immunology , pathology , thrombin , platelet
Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin‐like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion‐induced liver damage in a dose‐dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage.