Indoxyl sulfate‐induced calcification of vascular smooth muscle cells via the PI3K/Akt/NF‐κB signaling pathway. Issue 12 (25th August 2019)

• Record Type: Journal Article
• Authors: He, Xin; Jiang, Hongli; Gao, Fanfan; Liang, Shanshan; Wei, Meng; Chen, Lei
• Is Part Of: Microscopy research and technique. Volume 82:Issue 12(2019)
• Page Start: 2000
• Page End: 2006
• Publication Date: 2019-08-25
• Subjects: chronic kidney disease -- indoxyl sulfate -- nuclear factor‐kappa B -- osteogenic differentiation; Electron microscopy -- Technique -- Periodicals; Microscopy -- Periodicals; Microscopy -- Technique -- Periodicals; 502.825
• DOI: 10.1002/jemt.23369
• Languages: English
• ISSNs: 1059-910X

Abstract

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) is a representative protein‐bound uremic toxin in CKD patients, which has been recognized as a major risk factor for VC. Recent studies have demonstrated that nuclear factor‐kappa B (NK‐κB) is highly activated in the chronic inflammation conditions of CKD patients and participated in the pathogenesis of VC. However, whether NK‐κB is involved in the progression of IS‐induced VC remains without elucidation. Here, we showed that NK‐κB activity was increased in the IS‐induced calcification of human aortic smooth muscle cells (HASMCs). Blocking the NK‐κB with a selective inhibitor (Bay‐11‐7082) significantly relieved the osteogenic transdifferentiation of HASMCs, characterized by the downregulation of early osteogenic‐specific marker, core‐binding factor alpha subunit 1 (Cbfα1), and upregulation of smooth muscle α‐actin (α‐SMA), 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‐κB and osteogenic differentiation of HASMCs. Together, these results suggest that PI3K/Akt/NK‐κB signaling plays an important role in the pathogenesis of osteogenic transdifferentiation induced by IS. Abstract : According to the transcriptome analysis and enrichment KEGG pathway in our study, we have showed that IS‐induced osteogenic differentiation and calcification of human aortic smooth muscle cells via PI3K/Akt/NF‐κB signaling pathway.