4.5 Article

The fifth epidermal growth factor-like region of thrombomodulin exerts cytoprotective function and prevents SOS in a murine model

Journal

BONE MARROW TRANSPLANTATION
Volume 52, Issue 1, Pages 73-79

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2016.195

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Funding

  1. Adaptable and Seamless Technology Transfer Program through target-driven RD
  2. JST
  3. SENSHIN Medical Research Foundation
  4. KAKENHI [26461406]
  5. Grants-in-Aid for Scientific Research [16H02997, 26461406] Funding Source: KAKEN

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The present study found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) possesses the cytoprotective function in association with an increase in levels of anti-apoptotic myeloid cell leukemia-1 protein in an activated protein C-independent manner in human umbilical vein endothelial cells (HUVECs). Importantly, TME5 counteracted calcineurin inhibitor-induced vascular permeability and successfully prevented monocrotaline-induced sinusoidal obstruction syndrome (SOS) in a murine model. Taken together, TME5 may be useful for preventing or treating lethal complications that develop after hematopoietic stem cell transplantation such as SOS and thrombotic microangiopathy in which endothelial cell damage has a role.

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