Restoration of microRNA-30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy.
Animals
Aorta
/ metabolism
Autophagy
/ genetics
Beclin-1
/ genetics
Core Binding Factor Alpha 1 Subunit
/ genetics
Epigenomics
Gene Expression Regulation
/ genetics
Glycerophosphates
Homeodomain Proteins
/ genetics
Humans
Membrane Potential, Mitochondrial
/ genetics
MicroRNAs
/ genetics
Muscle, Smooth, Vascular
/ metabolism
Myocytes, Smooth Muscle
/ metabolism
Osteoblasts
/ metabolism
Rats
Renal Insufficiency, Chronic
/ genetics
SOX9 Transcription Factor
/ genetics
Signal Transduction
/ genetics
TOR Serine-Threonine Kinases
/ genetics
Vascular Calcification
/ genetics
autophagy
chronic kidney disease
high phosphorus
microRNA-30b
vascular calcification
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
24
10
2018
accepted:
21
12
2018
pubmed:
1
2
2019
medline:
27
5
2020
entrez:
1
2
2019
Statut:
ppublish
Résumé
Pathological calcification represents an event that consequently leads to a distinct elevation in the morbidity and mortality of patients with chronic kidney disease (CKD) in addition to strengthening its correlation with hyperphosphatemia. Epigenomic regulation by specific microRNAs (miRNAs) is reported to be involved in ectopic calcification. However, the finer molecular mechanisms governing this event remain unclear. Hence, this study aimed to identify the potential miRNAs involved in vascular calcification (VC) development and progression. Initially, mitochondrial membrane potential (MMP), autophagy-specific markers (LC3II/LC3I and Beclin1) and phenotype-specific markers of osteoblasts (runt-related transcription factor 2 and Msx2) were measured to evaluate autophagy and VC in β-glycerophosphate-induced vascular smooth muscle cells (VSMCs) with either miR-30b restoration or miR-30b knockdown performed in vitro. The VC in vivo was represented by calcified nodule formation in the aorta of the rats undergoing 5/6 nephrectomy followed by a 1.2% phosphorus diet using Alizarin Red staining. SOX9 was verified as the target of miR-30b according to luciferase activity determination. Restoration of miR-30b was revealed to markedly diminish the expression of SOX9 while acting to inhibit activation of the mTOR signaling pathway. Knockdown of miR-30b reduced MMP and autophagy, elevated VC, and suppressed the presence of rapamycin (an inhibitor of the mTOR signaling pathway). In addition, upregulated expression of miR-30b attenuated VC in vivo. Taken together, the key findings of this study identified the inhibitory role of miR-30b in VC, presenting an enhanced understanding of miRNA as a therapeutic target to curtail progressive VC in hyperphosphatemia of CKD.
Substances chimiques
Beclin-1
0
Core Binding Factor Alpha 1 Subunit
0
Glycerophosphates
0
Homeodomain Proteins
0
MIRN30b microRNA, human
0
MSX2 protein
0
MicroRNAs
0
Runx2 protein, rat
0
SOX9 Transcription Factor
0
Sox9 protein, rat
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
beta-glycerophosphoric acid
WWH06G87W6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14306-14318Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019 Wiley Periodicals, Inc.