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

Arcidiacono, Maria Vittoria, Carrillo-López, Natalia, Panizo, Sara, Castro-Grattoni, Anabel L., Valcheva, Petya, Ulloa, Catalina, Rodríguez-Carrio, Javier, Cardus Figueras, Anna, Quirós-Caso, Covadonga, Martínez-Arias, Laura, Martínez-Salgado, Carlos, Motilva, María José, Rodriguez-Suarez, Carmen, Cannata-Andía, Jorge B. and Dusso, Adriana S. 2019. Barley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibition. Scientific Reports 9 (1) , 17810. 10.1038/s41598-019-54306-8

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

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 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Date of First Compliant Deposit:	11 December 2019
Date of Acceptance:	6 November 2019
Last Modified:	03 May 2023 15:54
URI:	https://orca.cardiff.ac.uk/id/eprint/127475

Citation Data

Cited 10 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item