MiR-30c-5p regulates adventitial progenitor cells differentiation to vascular smooth muscle cells through targeting OPG

Background As the most important component of the vascular wall, vascular smooth muscle cells (VSMCs) participate in the pathological process by phenotype transformation or differentiation from stem/progenitor cells. The main purpose of this study was to reveal the role and related molecular mechani...

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Vydáno v:	Stem cell research & therapy Ročník 12; číslo 1; s. 67 - 14
Hlavní autoři:	Zhang, Qing, Chen, Ting, Zhang, Yun, Lyu, Lingxia, Zhang, Bohuan, Huang, Chengchen, Zhou, Xuhao, Wu, Yutao, Li, Zhoubin
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 19.01.2021 BioMed Central Ltd Springer Nature B.V BMC
Témata:	3' Untranslated regions Actin Analysis Arteries Arteriosclerosis Bioinformatics Biomedical and Life Sciences Biomedical Engineering and Bioengineering Bone morphogenetic proteins Cell Biology Cell Differentiation Cell Proliferation Cells, Cultured Chromosome 5 Cytology Differentiation Humans Hypertension Laboratory animals Life Sciences MicroRNAs MicroRNAs - genetics Migration MiR-30c-5p miRNA mRNA Muscle, Smooth, Vascular Myocytes, Smooth Muscle Myosin OPG Osteoprotegerin Phenotypes Plasmids Progenitor cells Proteins Regenerative Medicine/Tissue Engineering Reporter gene RNA siRNA Smooth muscle Stem Cells Thermal cycling Transfection Transforming growth factor-b1 Transforming growth factors Vascular progenitor cells Vascular smooth muscle cells Veins & arteries United Kingdom > UK United States > US China Japan MiR-30c-5p Vascular progenitor cells Differentiation Vascular smooth muscle cells OPG
ISSN:	1757-6512, 1757-6512
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Shrnutí:	Background As the most important component of the vascular wall, vascular smooth muscle cells (VSMCs) participate in the pathological process by phenotype transformation or differentiation from stem/progenitor cells. The main purpose of this study was to reveal the role and related molecular mechanism of microRNA-30c-5p (miR-30c-5p) in VSMC differentiation from adventitial progenitor cells expressing stem cell antigen-1(Sca-1). Methods In this study, we detected the expression of miR-30c-5p in human normal peripheral arteries and atherosclerotic arteries. In vitro, a stable differentiation model from adventitial Sca-1 + progenitor cells to VSMCs was established using transforming growth factor-β1 (TGF-β1) induction and the expression of miR-30c-5p during the process was observed. Then, we explored the effect of miR-30c-5p overexpression and inhibition on the differentiation from adventitial Sca-1 + progenitor cells to VSMCs. The target genes of miR-30c-5p were identified by protein chip and biological analyses and the expression of these genes in the differentiation process were detected. Further, the relationship between the target gene and miR-30c-5p and its effect on differentiation were evaluated. Finally, the co-transfection of miR-30c-5p inhibitor and small interfering RNA (siRNA) of the target gene was implemented to verify the functional target gene of miR-30c-5p during the differentiation from adventitial Sca-1 + progenitor cells to VSMCs, and the dual-luciferase reporter gene assay was performed to detect whether the mRNA 3′untranslated region (UTR) of the target gene is the direct binding site of miR-30c-5p. Results The expression of miR-30c-5p in the human atherosclerotic arteries was significantly lower than that in the normal arteries. During the differentiation from adventitial Sca-1 + progenitor cells to VSMCs, the expression of VSMC special markers including smooth muscle α-actin (SMαA), smooth muscle-22α (SM22α), smooth muscle myosin heavy chain (SMMHC), and h1-caponin increased accompanied with cell morphology changing from elliptic to fusiform. Meanwhile, the expression of miR-30c-5p decreased significantly. In functional experiments, overexpression of miR-30c-5p inhibited SMαA, SM22α, SMMHC, and h1-caponin at the mRNA and protein levels. In contrast, inhibition of miR-30c-5p promoted the expression of SMαA, SM22α, SMMHC, and h1-caponin. The target gene, osteoprotegerin (OPG), was predicted through protein chip and bioinformatics analyses. Overexpression of miR-30c-5p inhibited OPG expression while inhibition of miR-30c-5p had an opposite effect. Co-transfection experiments showed that low expression of OPG could weaken the promotion effect of miR-30c-5p inhibitor on the differentiation from adventitial Sca-1 + progenitor cells to VSMCs and the dual-luciferase reporter gene assay demonstrated that miR-30c-5p could target the mRNA 3′UTR of OPG directly. Conclusions This study demonstrates that miR-30c-5p expression was significantly decreased in atherosclerotic arteries and miR-30c-5p inhibited VSMC differentiation from adventitial Sca-1 + progenitor cells through targeting OPG, which may provide a new target for the treatment of VSMCs-associated diseases.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1757-6512 1757-6512
DOI:	10.1186/s13287-020-02127-2