Restoration of microRNA-30b expression alleviates vascular calcification through the mTOR signaling pathway and autophagy.


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
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.

Identifiants

pubmed: 30701530
doi: 10.1002/jcp.28130
doi:

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

14306-14318

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2019 Wiley Periodicals, Inc.

Auteurs

Tian-Hua Xu (TH)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Xiao-Bo Qiu (XB)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Zi-Tong Sheng (ZT)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Yi-Ran Han (YR)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Jian Wang (J)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Bin-Yao Tian (BY)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

Li Yao (L)

Department of Nephrology, The First Hospital of China Medical University, Shenyang, P. R. China.

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Classifications MeSH