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

Abstract:

: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.

journal_name

J Cell Physiol

authors

Xu TH,Qiu XB,Sheng ZT,Han YR,Wang J,Tian BY,Yao L

doi

10.1002/jcp.28130

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

14306-14318

issue

8

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

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