{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:46Z","timestamp":1760145946666,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}]},{"name":"Collaborative Research Centre PolyTarget 1278-2021","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institutes for Health Research (CIHR)","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}]},{"name":"CanVECTOR","award":["CO912\/2-1","316213987","03Z22JN12","03COV07"],"award-info":[{"award-number":["CO912\/2-1","316213987","03Z22JN12","03COV07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hemolytic-uremic syndrome (HUS) is a rare complication of an infection with Shiga toxin (Stx)-producing Escherichia coli (STEC-HUS), characterized by severe acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia, and specific therapy is still lacking. Thrombomodulin (TM) is a multi-domain transmembrane endothelial cell protein and its N-terminal domain has been implicated in the pathophysiology of some cases of HUS. Indeed, the administration of recombinant human TM (rhTM) may have efficacy in HUS. We used a Stx-based murine model of HUS to characterize the role of the N-terminal domain of TM. We show that mice lacking that domain (TMLed (\u2212\/\u2212)) are more sensitive to Stx, with enhanced HUS progression seen at 4 days and increased mortality at 7 days post-HUS induction. In spite of these changes, renal function was less affected in surviving Stx-challenged TMLed (\u2212\/\u2212) mice compared to their wild-type counterparts TMLed (+\/+) at 7 days. Contrary to few clinical case reports from Japan, the administration of rhTM (0.06 mg\/kg) to wild-type mice (C57BL\/6J) with HUS did not protect against disease progression. This overall promising, but also contradictory body of evidence, requires further systematic preclinical and clinical investigations to clarify the role of TM in HUS as a potential therapeutic strategy.<\/jats:p>","DOI":"10.3390\/toxins16090409","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T10:49:48Z","timestamp":1726829388000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of the N-Terminal Domain of Thrombomodulin and the Potential of Recombinant Human Thrombomodulin as a Therapeutic Intervention for Shiga Toxin-Induced Hemolytic-Uremic Syndrome"],"prefix":"10.3390","volume":"16","author":[{"given":"Sarah","family":"Kr\u00f6ller","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Schober","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Krieg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Dennhardt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Pirschel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kiehntopf","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, 07747 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0081-0305","authenticated-orcid":false,"given":"Edward M.","family":"Conway","sequence":"additional","affiliation":[{"name":"Centre for Blood Research, Life Sciences Institute, Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-0006","authenticated-orcid":false,"given":"Sina M.","family":"Coldewey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany"},{"name":"Septomics Research Center, Jena University Hospital, 07745 Jena, Germany"},{"name":"Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3390\/toxins3060626","article-title":"Shiga toxin interaction with human intestinal epithelium","volume":"3","year":"2011","journal-title":"Toxins"},{"doi-asserted-by":"crossref","unstructured":"St\u00e5hl, A.-L., Arvidsson, I., Johansson, K.E., Chromek, M., Rebetz, J., Loos, S., Kristoffersson, A.-C., B\u00e9k\u00e1ssy, Z.D., M\u00f6rgelin, M., and Karpman, D. 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