{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:09:41Z","timestamp":1785312581677,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["26fk0210156h0003"],"award-info":[{"award-number":["26fk0210156h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The therapeutic significance of recombinant a disintegrin\u2010like and metalloprotease with thrombospondin type 1 motif 13 (rADAMTS13) in acute\u2010on\u2010chronic liver failure (ACLF) remains unclear. We aimed to investigate the therapeutic effects of rADAMTS13 in a murine model of ACLF\u2010like liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6J mice were subjected to chronic carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      ) administration followed by acute CCl\n                      <jats:sub>4<\/jats:sub>\n                      and lipopolysaccharide challenge to induce ACLF\u2010like liver injury. Mice were assigned to control, ACLF, and ACLF\u00a0+\u00a0rADAMTS13 groups. Plasma ADAMTS13 activity, VWF antigen, platelet counts, hepatic microcirculatory blood flow, histological changes, and hepatic gene expression were evaluated. Endothelial tube formation assays were performed using human umbilical vein endothelial cells (HUVECs) under oxidative stress conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      rADAMTS13 treatment improved plasma ADAMTS13 activity, reduced VWF antigen levels, and attenuated intrahepatic platelet accumulation in ACLF mice. These changes were accompanied by improved hepatic microcirculatory blood flow, reduced plasma transaminase levels, and decreased hepatic necrosis and macrophage infiltration. rADAMTS13 also reduced oxidative stress\u2010related markers and fibrosis\u2010related readouts in the acute setting. The treatment was associated with increased hepatic CD34 staining, upregulation of\n                      <jats:italic>Vegfa<\/jats:italic>\n                      , and increased regeneration\u2010related markers, including Ki67, A6,\n                      <jats:italic>Hgf<\/jats:italic>\n                      , and\n                      <jats:italic>Egf<\/jats:italic>\n                      . In vitro, rADAMTS13 partially restored impaired tube formation and increased\n                      <jats:italic>VEGFA<\/jats:italic>\n                      and\n                      <jats:italic>VEGFR2<\/jats:italic>\n                      expression in HUVECs exposed to oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>rADAMTS13 attenuated liver injury in a murine ACLF\u2010like model and was associated with restoration of the ADAMTS13\/VWF axis, improved hepatic microcirculation, and increased angiogenesis\u2010 and regeneration\u2010related responses. These findings suggest that rADAMTS13 may represent a potential therapeutic approach for ACLF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70253","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:50:27Z","timestamp":1785311427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant ADAMTS13 Ameliorates Liver Injury and Improves Hepatic Microcirculation in a Murine Acute\u2010on\u2010Chronic Liver Failure Model"],"prefix":"10.1111","author":[{"given":"Jun\u2010ichi","family":"Hanatani","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6295-3283","authenticated-orcid":false,"given":"Norihisa","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-6759","authenticated-orcid":false,"given":"Kosuke","family":"Kaji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Takami","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nara Medical University  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nara Medical University  Kashihara Nara 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