{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:41:43Z","timestamp":1777999303616,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T00:00:00Z","timestamp":1586044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thrombomodulin (TM) is a single transmembrane, multidomain glycoprotein receptor for thrombin, and is best known for its role as a cofactor in a clinically important natural anticoagulant pathway. In addition to its anticoagulant function, TM has well-defined anti-inflammatory properties. Soluble TM levels increase significantly in the plasma of septic patients; however, the possible involvement of recombinant human soluble TM (rTM) transduction in the pathogenesis of lipopolysaccharide (LPS)-induced nephrotoxicity, including acute kidney injury (AKI), has remained unclear. Mice were injected intraperitoneally with 15 mg\/kg LPS. rTM (3 mg\/kg) or saline was administered to the animals before the 3 and 24 h LPS-injection. At 24 and 48 h, blood urea nitrogen, the inflammatory cytokines in sera and kidney, and histological findings were assessed. Cell activation and apoptosis signal was assessed by Western blot analysis. In this study using a mouse model of LPS-induced AKI, we found that rTM attenuated renal damage by reducing both cytokine and cell activation and apoptosis signals with the accumulation of CD4+ T-cells, CD11c+ cells, and F4\/80+ cells via phospho c-Jun activations and Bax expression. These findings suggest that the mechanism underlying these effects of TM may be mediated by a reduction in inflammatory cytokine production in response to LPS. These molecules might thereby provide a new therapeutic strategy in the context of AKI with sepsis.<\/jats:p>","DOI":"10.3390\/ijms21072519","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T06:10:28Z","timestamp":1586153428000},"page":"2519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Protective Effects of Recombinant Human Soluble Thrombomodulin on Lipopolysaccharide-Induced Acute Kidney Injury"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-1519","authenticated-orcid":false,"given":"Yuji","family":"Nozaki","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhai","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Niki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Funauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000102085","article-title":"Emerging biomarkers of acute kidney injury","volume":"156","author":"Devarajan","year":"2007","journal-title":"Contrib. 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