This work was supported by European Union FEDER funds, Fondo de Investigación Sanitaria (PI14/01452, PI16/00113, PI17/02181, PI19/00532) from Instituto de Salud Carlos III (ISCIII), Plan de Ciencia, Tecnología e Innovación 2013-2017 del Principado de Asturias (GRUPIN14-028 and IDI/2018/000152) from Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT), Red de Investigación Renal-RedInREN (RETIC REDINREN RD16/0009) from ISCIII, and by Sociedad Asturiana Fomento Investigaciones Metabólicas (SAFIM). JR-C is supported by postdoctoral contracts from the Juan de la Cierva (IJCI-2017-32070, Ministerio de Ciencia e Innovación, Spain) and Sara Borrell programs (CD19/00120, from ISCIII). NC-L is supported by GRUPIN14-028 and IDI/2018/000152, and AD is supported by Asociación Investigación de Fisiología Aplicada and ISPA. BM-C was supported by ISCIII-ISPA (PI17/00384) and by a graduate fellowship from the Gobierno del Principado de Asturias (Severo Ochoa program BP19-057).
Tis work was supported by European Union FEDER funds, "Fondo de Investigación Sanitaria" (PI16/00113, PI14/01452, PI17/02181) from Instituto de Salud Carlos III (ISCIII), Plan de Ciencia, Tecnología e Innovación 2013–2017 del Principado de Asturias (GRUPIN14-028 and IDI/2018/000152) from Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT), Red de Investigación Renal-RedInREN (RETIC REDINREN RD16/0009) from ISCIII, and by Sociedad Asturiana Fomento Investigaciones Metabólicas (SAFIM). J.R.-C. is supported by postdoctoral contracts from the "Juan de la Cierva" program (FJCI-2015-23849 and IJCI-2017- 32070), NC-L is supported by GRUPIN14-028 and IDI/2018/000152, and ASD is supported by Asociación Investigación de Fisiología Aplicada and ISPA.
A grant to A.S.D. and M.J.M. from IRB Lleida 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 2A/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).
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. ; A 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).
