title: The fifth epidermal growth factor-like region of thrombomodulin exerts cytoprotective function and prevents SOS in a murine model.
abstract: 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.
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.|Department of Hematology, Fukushima Medical University, Fukushima City, Fukushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikezoe
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nishioka
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Furihata
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yurimoto
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Medial Affairs Department, Asahi Kasei Pharma, Kanda Jinbocho, Chiyoda-ku, Tokyo, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Honda
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D004815:Epidermal Growth Factor; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D016686:Monocrotaline / Q000009:adverse effects / Q000494:pharmacology; D000072417:Protein Domains; D018180:Thrombomodulin / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics
chemical_list: C546931:THBD protein, human; C569169:THBD protein, mouse; D018180:Thrombomodulin; D004815:Epidermal Growth Factor; D016686:Monocrotaline