title: Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification.
abstract: Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg(2+)) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg(2+) on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg(2+) chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg(2+) restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg(2+). As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg(2+) with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.
authors.affiliation: INSERM U 1088, CURS, University of Picardie Jules Verne, Amiens, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Louvet
authors.affiliation: INSERM U 1088, CURS, University of Picardie Jules Verne, Amiens, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Metzinger
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Büchel
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Steppan
authors.affiliation: Division of Nephrology, Ambroise Paré University Hospital, APHP, University of Paris Ouest-Versailles-St-Quentin-en-Yvelines (UVSQ), Boulogne-Billancourt, Paris, France; INSERM U 1018, Research Centre in Epidemiology and Population Health (CESP) Team 5, Villejuif, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage*; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000008:administration & dosage*; D051898:Smad1 Protein / Q000378:metabolism*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*; D061205:Vascular Calcification / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D010710:Phosphates; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D008274:Magnesium; D002118:Calcium