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Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition.


ABSTRACT: In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNF?-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory ?-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley ?-glucans (B?glucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNF?, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for ?-interferon. In hyperphosphatemic rat CKD, dietary B?glucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNF?-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, B?glucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNF? and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving B?glucans internalization. Thus, dietary B?glucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.

SUBMITTER: Arcidiacono MV 

PROVIDER: S-EPMC6882851 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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