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

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2019-11-28Author
Arcidiacono, Maria V.
Carrillo-López, Natalia
Panizo García, Sara
Valcheva, Petya
Ulloa, Catalina
Rodríguez-Carrio, Javier
Cardús i Figueras, Anna
Quirós-Caso, Covadonga
Martínez-Arias, Laura
Martínez-Salgado, Carlos
Rodríguez Suárez, Carmen
Cannata-Andía, Jorge B.
Dusso Rosso, Adriana
Suggested citation
Arcidiacono, Maria V.;
Carrillo-López, Natalia;
Panizo García, Sara;
Castro-Grattoni, Anabel L.;
Valcheva, Petya;
Ulloa, Catalina;
...
Dusso Rosso, Adriana.
(2019)
.
Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition.
Scientific Reports, 2019, vol. 9, article number 17810.
https://doi.org/10.1038/s41598-019-54306-8.
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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 TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα 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 Bβglucans internalization. Thus, dietary Bβglucans 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.