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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      ADAM17 Protein/*antagonists & inhibitors ; Hordeum/*chemistry ; Renal Insufficiency, Chronic/*diet therapy ; Sphingomyelin Phosphodiesterase/*antagonists & inhibitors ; Vascular Calcification/*diet therapy ; beta-Glucans/*therapeutic use; Adult ; Animals ; Disease Models, Animal ; Female ; Healthy Volunteers ; Humans ; Inflammation/diet therapy ; Male ; Mice ; Middle Aged ; RAW 264.7 Cells ; Rats ; Rats, Sprague-Dawley ; Young Adult ; beta-Glucans/pharmacology
    • 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.
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    • Accession Number:
      0 (beta-Glucans)
      EC 3.1.4.12 (SMPD3 protein, human)
      EC 3.1.4.12 (Smpd3 protein, mouse)
      EC 3.1.4.12 (Smpd3 protein, rat)
      EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
      EC 3.4.24.86 (ADAM17 Protein)
      EC 3.4.24.86 (ADAM17 protein, human)
      EC 3.4.24.86 (Adam17 protein, mouse)
      EC 3.4.24.86 (Adam17 protein, rat)
    • Publication Date:
      Date Created: 20191130 Date Completed: 20201118 Latest Revision: 20210110
    • Publication Date:
      20221213
    • Accession Number:
      PMC6882851
    • Accession Number:
      10.1038/s41598-019-54306-8
    • Accession Number:
      31780737