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 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.

• Authors: Maria Vittoria Arcidiacono, Natalia Carrillo-López, Sara Panizo, Anabel L Castro-Grattoni, Petya Valcheva, Catalina Ulloa, Javier Rodríguez-Carrio, Anna Cardús, Covadonga Quirós-Caso, Laura Martínez-Arias, Carlos Martínez-Salgado, María José Motilva, Carmen Rodriguez-Suarez, Jorge B Cannata-Andía, Adriana S Dusso
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 17810 (11 28 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31780737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• beta-Glucans
• SMPD3 protein, human
• Smpd3 protein, mouse
• Smpd3 protein, rat
• Sphingomyelin Phosphodiesterase
• ADAM17 Protein
• ADAM17 protein, human
• Adam17 protein, mouse
• Adam17 protein, rat

Topics

• ADAM17 Protein (antagonists & inhibitors)
• Adult
• Animals
• Disease Models, Animal
• Female
• Healthy Volunteers
• Hordeum (chemistry)
• Humans
• Inflammation (diet therapy)
• Male
• Mice
• Middle Aged
• RAW 264.7 Cells
• Rats
• Rats, Sprague-Dawley
• Renal Insufficiency, Chronic (diet therapy)
• Sphingomyelin Phosphodiesterase (antagonists & inhibitors)
• Vascular Calcification (diet therapy)
• Young Adult
• beta-Glucans (pharmacology, therapeutic use)