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Indoxyl sulfate (IS) is a representative protein\u2010bound uremic toxin in CKD patients, which has been recognized as a major risk factor for VC. Recent studies have demonstrated that nuclear factor\u2010kappa B (NK\u2010\u03baB) is highly activated in the chronic inflammation conditions of CKD patients and participated in the pathogenesis of VC. However, whether NK\u2010\u03baB is involved in the progression of IS\u2010induced VC remains without elucidation. Here, we showed that NK\u2010\u03baB activity was increased in the IS\u2010induced calcification of human aortic smooth muscle cells (HASMCs). Blocking the NK\u2010\u03baB with a selective inhibitor (Bay\u201011\u20107082) significantly relieved the osteogenic transdifferentiation of HASMCs, characterized by the downregulation of early osteogenic\u2010specific marker, core\u2010binding factor alpha subunit 1 (Cbf\u03b11), and upregulation of smooth muscle \u03b1\u2010actin (\u03b1\u2010SMA), a specific vascular smooth muscle cell marker. Besides, IS stimulated the activation of PI3K\/Akt signaling. Furthermore, LY294002, a specific inhibitor of PI3K\/Akt pathway, attenuated the activation of NK\u2010\u03baB and osteogenic differentiation of HASMCs. Together, these results suggest that PI3K\/Akt\/NK\u2010\u03baB signaling plays an important role in the pathogenesis of osteogenic transdifferentiation induced by IS.<\/jats:p>","DOI":"10.1002\/jemt.23369","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:29:55Z","timestamp":1566779395000},"page":"2000-2006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Indoxyl sulfate\u2010induced calcification of vascular smooth muscle cells via the PI3K\/Akt\/NF\u2010\u03baB signaling pathway"],"prefix":"10.1002","volume":"82","author":[{"given":"Xin","family":"He","sequence":"first","affiliation":[{"name":"Dialysis Department of Nephrology Hospital First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Jiang","sequence":"additional","affiliation":[{"name":"Dialysis Department of 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