1. The microRNA miR-134-5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells.
- Author
-
Choe N, Shin S, Joung H, Ryu J, Kim YK, Ahn Y, Kook H, and Kwon DH
- Subjects
- 3' Untranslated Regions, Animals, Aorta, Thoracic cytology, Cell Line, Computer Simulation, Core Binding Factor Alpha 1 Subunit biosynthesis, Core Binding Factor Alpha 1 Subunit genetics, Core Binding Factor Alpha 1 Subunit immunology, Down-Regulation, Gene Expression Regulation, Genes, Reporter, Histone Deacetylases biosynthesis, Histone Deacetylases genetics, MicroRNAs genetics, Microarray Analysis, Muscle, Smooth, Vascular cytology, Osteoprotegerin biosynthesis, Osteoprotegerin genetics, Phosphates toxicity, RNA, Small Interfering genetics, RNA, Small Interfering pharmacology, Rats, Rats, Sprague-Dawley, Recombinant Fusion Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Transfection, Vascular Calcification genetics, Vascular Calcification metabolism, Vascular Calcification prevention & control, Calcium metabolism, Histone Deacetylases drug effects, MicroRNAs physiology, Myocytes, Smooth Muscle metabolism, Vascular Calcification etiology
- Abstract
Calcium deposition in vascular smooth muscle cells (VSMCs) is a form of ectopic ossification in blood vessels. It can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that the microRNA miR-134-5p potentiates inorganic phosphate (Pi)-induced calcium deposition in VSMCs by inhibiting histone deacetylase 5 (HDAC5). Using miRNA microarray analysis of Pi-treated rat VSMCs, we first selected miR-134-5p for further evaluation. Quantitative RT-PCR confirmed that miR-134-5p was increased in Pi-treated A10 cells, a rat VSMC line. Transfection of miR-134-5p mimic potentiated the Pi-induced increase in calcium contents. miR-134-5p increased the amounts of bone runt-related transcription factor 2 (RUNX2) protein and bone morphogenic protein 2 (BMP2) mRNA in the presence of Pi but decreased the expression of osteoprotegerin (OPG). Bioinformatic analysis showed that the HDAC5 3'untranslated region (3'UTR) was one of the targets of miR-134-5p. The luciferase construct containing the 3'UTR of HDAC5 was down-regulated by miR-134-5p mimic in a dose-dependent manner in VSMCs. Overexpression of HDAC5 mitigated the calcium deposition induced by miR-134-5p. Our results suggest that a Pi-induced increase of miR-134-5p may cause vascular calcification through repression of HDAC5., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
- View/download PDF