{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:23:25Z","timestamp":1787729005757,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272185"],"award-info":[{"award-number":["82272185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Septic cardiomyopathy is characterized by acute cardiac dysfunction, while sustained inflammatory and extracellular matrix remodeling may contribute to subsequent myocardial fibrosis and impaired cardiac recovery. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) has been linked to fibrotic remodelling, but its role in septic cardiac injury remains unclear. Here, we show that\n                      <jats:italic>Adamts4<\/jats:italic>\n                      is upregulated in LPS\u2010induced septic mouse hearts and is predominantly induced in cardiac fibroblasts. Using three fibroblast\u2010lineage Adamts4 knockout models, we demonstrate that Adamts4 deletion attenuates LPS\u2010induced cardiac dysfunction, inflammation and fibrosis, whereas Tcf21\u2010lineage fibroblast\n                      <jats:italic>Adamts4<\/jats:italic>\n                      overexpression aggravates these changes. Mechanistically, ADAMTS4 interacts with thrombospondin\u20101 (TSP1) and promotes its catalytic activity\u2010dependent proteolytic processing. The 236\u2013246 amino acid region of TSP1 is required for fragment generation and fibroblast activation. TSP1 processing further activates TGF\u2010\u03b2\/Smad and NF\u2010\u03baB signalling, promoting myofibroblast activation and extracellular matrix deposition. These findings identify ADAMTS4 as a fibroblast\u2010centred driver of septic cardiac fibrosis and suggest that targeting the ADAMTS4\u2010TSP1 axis may offer therapeutic potential for septic cardiomyopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>ADAMTS4 is induced predominantly in cardiac fibroblasts after LPS challenge<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Fibroblast\u2010lineage Adamts4 deletion attenuates LPS\u2010induced cardiac dysfunction and fibrosis<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The TSP1 236\u2010246 aa region is required for efficient ADAMTS4\u2010dependent processing<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>ADAMTS4\u2010dependent TSP1 processing activates TGF\u2010\u03b2\/Smad and NF\u2010\u03baB signalling in fibroblasts.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70769","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:25:59Z","timestamp":1785993959000},"source":"Crossref","is-referenced-by-count":0,"title":["ADAMTS4 mediates LPS\u2010induced cardiac injury and myocardial fibrosis through proteolytic cleavage of TSP1"],"prefix":"10.1002","volume":"16","author":[{"given":"Zhe\u2010Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Yan","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2184-8549","authenticated-orcid":false,"given":"Xin","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6761-3158","authenticated-orcid":false,"given":"Wei","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Yang","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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