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Vascular extracellular matrix (ECM) proteins have been demonstrated to regulate vascular calcification. ECM protein thrombospondin 1 (THBS1\/TSP\u20101) plays a critical role in the regulation of vascular diseases. However, whether THBS1 is involved in vascular calcification in CKD patients remains unclear. In this study, RNA sequencing datasets from the Gene Expression Omnibus (GEO) database GSE146638 showed that THBS1 was upregulated in the aortas of CKD rats. Enzyme\u2010linked immunosorbent assay (elisa) revealed that serum THBS1 levels were increased in CKD patients with thoracic calcification. Western blotting and immunofluorescence analysis showed that THBS1 expression was increased in calcified vascular smooth muscle cells (VSMCs) and arteries. <jats:italic>THBS1<\/jats:italic> knockdown exacerbated rat VSMC calcification induced by high phosphorus and calcium, as shown by Alizarin red staining and calcium content assays. Conversely, <jats:italic>THBS1<\/jats:italic> overexpression attenuated VSMC calcification and abdominal aortic calcification in rats with CKD. Moreover, addition of recombinant THBS1 protein inhibited calcification of VSMC<jats:sub>S<\/jats:sub> and human arterial rings. Smooth muscle cell\u2010specific knockout of <jats:italic>THBS1<\/jats:italic> mice treated with vitamin D3 displayed aggravated aortic calcification. Mechanistically, the protein\u2013protein interaction database STRING (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/string-db.org\/\">http:\/\/string-db.org\/<\/jats:ext-link>) analysis and coimmunoprecipitation assays revealed THBS1 bound to integrin \u03b23. Reduction of integrin \u03b23 levels abrogated the protective effect of THBS1 on vascular calcification. RNA\u2010seq analysis revealed that <jats:italic>THBS1<\/jats:italic> overexpression modulated the nuclear factor\u2010kappa B (NF\u2010\u03baB) signaling pathway. Of note, the inhibitory effect of <jats:italic>THBS1<\/jats:italic> overexpression on the NF\u2010\u03baB signal was abolished by knockdown of integrin \u03b23. In conclusion, THBS1 interacts with integrin \u03b23 to inhibit vascular calcification through suppression of NF\u2010\u03baB signal, suggesting a promising therapeutic target for vascular calcification in CKD. \u00a9 2025 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6417","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T08:02:15Z","timestamp":1741939335000},"page":"109-123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thrombospondin\u20101 binds to integrin \u03b23 to inhibit vascular calcification through suppression of <scp>NF<\/scp>\u2010<scp>\u03baB<\/scp> pathway"],"prefix":"10.1002","volume":"266","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0003-7463","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Laboratory of Heart Center, Heart Center, 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