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

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dc.contributor.authorArcidiacono, Maria V.
dc.contributor.authorCarrillo-López, Natalia
dc.contributor.authorPanizo García, Sara
dc.contributor.authorCastro-Grattoni, Anabel L.
dc.contributor.authorValcheva, Petya
dc.contributor.authorUlloa, Catalina
dc.contributor.authorRodríguez-Carrio, Javier
dc.contributor.authorCardús i Figueras, Anna
dc.contributor.authorQuirós-Caso, Covadonga
dc.contributor.authorMartínez-Arias, Laura
dc.contributor.authorMartínez-Salgado, Carlos
dc.contributor.authorMotilva Casado, Mª José
dc.contributor.authorRodríguez Suárez, Carmen
dc.contributor.authorCannata-Andía, Jorge B.
dc.contributor.authorDusso Rosso, Adriana
dc.date.accessioned2020-01-21T09:14:46Z
dc.date.available2020-01-21T09:14:46Z
dc.date.issued2019-11-28
dc.description.abstractIn 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.ca_ES
dc.description.sponsorshipA grant to A.S.D. and M.J.M. from IRBLleida and Agrotecnio Research collaborative projects from the Consell Social at Lleida University supported initial work, Instituto de Salud Carlos III and co-funded by European Union (ERDF/FEDER) (FIS PI11/00259, PI14/01452, PI17/02181), Plan de Ciencia, Tecnología e Innovación 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152), RedInRen from ISCIII (ISCIII-RETIC REDINREN RD16/0009). Investigator support included: NC-L by GRUPIN14-028 and IDI-2018-000152, LM-A by GRUPIN14-028, SP by FICYT; MVA and PV by Educational Grant 2 A/2015 from ERA-EDTA CKD-MBD Working Group; PV and AC by ERA-EDTA fellowships 2011 and 2012; JR-C by MINECO (“Juan de la Cierva” program, FJCI-2015-23849); A.S.D. by Asociación Investigación de Fisiología Aplicada. A.S.D. and M.J.M. are members of the Campus Iberus (Ebro Valley Campus of International Excellence).ca_ES
dc.identifier.doihttps://doi.org/10.1038/s41598-019-54306-8
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10459.1/67831
dc.language.isoengca_ES
dc.publisherSpringer Natureca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1038/s41598-019-54306-8ca_ES
dc.relation.ispartofScientific Reports, 2019, vol. 9, article number 17810ca_ES
dc.rightscc-by (c) Arcidiacono, Maria V. et al., 2019ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleBarley-ß-glucans reduce systemic inflammation, renal injury and aortic calcification through ADAM17 and neutral-sphingomyelinase2 inhibitionca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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