Open AccessThe microRNA miR‐134‐5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells
Author(s) -
Choe Nakwon,
Shin Sera,
Joung Hosouk,
Ryu Juhee,
Kim YoungKook,
Ahn Youngkeun,
Kook Hyun,
Kwon DukHwa
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15670
Subject(s) - histone deacetylase 5 , vascular smooth muscle , histone deacetylase , microrna , microbiology and biotechnology , endocrinology , transfection , medicine , chemistry , biology , histone , biochemistry , smooth muscle , gene
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.