The microRNA miR-134-5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells.
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.
['Choe|Nakwon|N|', 'Shin|Sera|S|', 'Joung|Hosouk|H|', 'Ryu|Juhee|J|', 'Kim|Young-Kook|YK|0000-0001-6434-2235', 'Ahn|Youngkeun|Y|', 'Kook|Hyun|H|0000-0002-0740-1806', 'Kwon|Duk-Hwa|DH|0000-0001-6424-0300']
D020413:3' Untranslated Regions D000818:Animals D001013:Aorta, Thoracic D002118:Calcium D002460:Cell Line D003198:Computer Simulation D050659:Core Binding Factor Alpha 1 Subunit D015536:Down-Regulation D005786:Gene Expression Regulation D017930:Genes, Reporter D006655:Histone Deacetylases D035683:MicroRNAs D046228:Microarray Analysis D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D053244:Osteoprotegerin D010710:Phosphates D034741:RNA, Small Interfering D051381:Rats D017207:Rats, Sprague-Dawley D011993:Recombinant Fusion Proteins D016415:Sequence Alignment D017386:Sequence Homology, Amino Acid D014162:Transfection D061205:Vascular Calcification
microRNA miR-134-5p histone deacetylase 5 vascular smooth muscle cells vascular calcification