Indoxyl sulfate‐induced calcification of vascular smooth muscle cells via the PI3K/Akt/NF‐κB signaling pathway

• DOI: 10.1002/jemt.23369
• Publication Date: 2019-08-26T04:29:55Z
• Authors: Xin He; Hongli Jiang; Fanfan Gao; Shanshan Liang; Meng Wei; Lei Chen
• Keywords: Transdifferentiation; Pathogenesis; Myofibroblast; LY294002

Abstract Vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD) and contributes to their high rate of cardiovascular mortality. Indoxyl sulfate (IS) a representative protein‐bound uremic toxin CKD patients, which has been recognized as major risk factor for VC. Recent studies have demonstrated that nuclear factor‐kappa B (NK‐κB) activated the inflammation conditions participated pathogenesis However, whether NK‐κB involved progression IS‐induced VC remains without elucidation. Here, we showed activity was increased human aortic smooth muscle cells (HASMCs). Blocking selective inhibitor (Bay‐11‐7082) significantly relieved osteogenic transdifferentiation HASMCs, characterized by downregulation early osteogenic‐specific marker, core‐binding alpha subunit 1 (Cbfα1), upregulation α‐actin (α‐SMA), specific vascular cell marker. Besides, IS stimulated activation PI3K/Akt signaling. Furthermore, LY294002, pathway, attenuated differentiation HASMCs. Together, these results suggest PI3K/Akt/NK‐κB signaling plays an important role induced IS.