{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:03:17Z","timestamp":1791378197553,"version":"4.3.2"},"reference-count":58,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health Medical Research Council","doi-asserted-by":"publisher","award":["GNT200799"],"award-info":[{"award-number":["GNT200799"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health Medical Research Council","doi-asserted-by":"publisher","award":["GNT2036460"],"award-info":[{"award-number":["GNT2036460"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation Vanguard","doi-asserted-by":"publisher","award":["106035"],"award-info":[{"award-number":["106035"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Westmead Medical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1\u2013CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5\/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated \u03b2-galactosidase activity, and activated phosphorylated ERK1\/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5\/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1\/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1\/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD.<\/jats:p>","DOI":"10.3390\/ijms27020755","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thrombospondin 1\u2013CD47 Signalling Modulates Vascular Smooth Muscle Cell Senescence in Chronic Kidney Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Katie","family":"Trinh","sequence":"first","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"},{"name":"Renal Medicine, Blacktown Hospital, Blacktown, NSW 2148, Australia"},{"name":"Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Coulter","sequence":"additional","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-8697","authenticated-orcid":false,"given":"Cuicui","family":"Xu","sequence":"additional","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia Chandra","family":"Sekar","sequence":"additional","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0834-2366","authenticated-orcid":false,"given":"Sohel M.","family":"Julovi","sequence":"additional","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"},{"name":"Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha M.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"},{"name":"Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Department of Renal and Transplantation Medicine, Westmead Hospital, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S80","DOI":"10.1046\/j.1523-1755.63.s84.1.x","article-title":"Morphology of the heart and arteries in renal failure","volume":"63","author":"Tyralla","year":"2003","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1159\/000327131","article-title":"Does uremia cause vascular dysfunction?","volume":"34","author":"Brunet","year":"2011","journal-title":"Kidney Blood Press. 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