Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

Loïc Louvet (1) , Laurent Metzinger (1) , Janine Buechel (2) , Sonja Steppan (2) , Ziad A. Massy (3, 4, 5)

1 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
2 Fresenius Medical Care [Bad Homburg]
3 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
4 Service Néphrologie/Dialyse [AP-HP Ambroise-Paré]
5 CESP - Centre de recherche en épidémiologie et santé des populations

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 (Mg2+) 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 Mg2+ on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+ 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 Mg2+ 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 Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+ 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.

Domaines: Sciences du Vivant [q-bio]

Loïc Louvet, Laurent Metzinger, Janine Buechel, Sonja Steppan, Ziad A. Massy. Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification. BioMed Research International , 2016, 2016, ⟨10.1155/2016/7419524⟩. ⟨hal-03584416⟩