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http://purl.uniprot.org/citations/27908889http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27908889http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Lineage-negative bone marrow cells (lin-BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin-BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin-BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin-BMCs is a critical step in understanding the process of vascular repair. The aim of this study was to characterize the role of the miR-146a-Polo-like kinase 2 (Plk2) network in regulating lin-BMC senescence, apoptosis, and their angiogenic capability.

Approach and results

Transcriptome analysis in lin-BMCs isolated from young and aged wild-type and ApoE-/- (apolipoprotein E) mice showed a significant age-associated increase in miR-146a expression. In silico analysis, expression study and Luciferase reporter assay established Plk2 as a direct target of miR-146a. miR-146a overexpression in young lin-BMCs inhibited Plk2 expression, resulting in increased senescence and apoptosis, via p16Ink4a/p19Arf and p53, respectively, as well as impaired angiogenic capacity in vitro and in vivo. Conversely, suppression of miR-146a in aged lin-BMCs increased Plk2 expression and rejuvenated lin-BMCs, resulting in decreased senescence and apoptosis, leading to improved angiogenesis.

Conclusions

(1) miR-146a regulates lin-BMC senescence and apoptosis by suppressing Plk2 expression that, in turn, activates p16Ink4a/p19Arf and p53 and (2) modulation of miR-146a or its target Plk2 may represent a potential therapeutic intervention to improve lin-BMC-mediated angiogenesis and vascular repair."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.116.308378"xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Chen E."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Deng S."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Zhu W."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Wei J."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Zhu S."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Chu X."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Ma Q."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Jia C."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Dong C."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Dykxhoorn D.M."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Macon C.J."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/author"Jayaweera D.T."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/pages"280-290"xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/title"MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression."xsd:string
http://purl.uniprot.org/citations/27908889http://purl.uniprot.org/core/volume"37"xsd:string
http://purl.uniprot.org/citations/27908889http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27908889
http://purl.uniprot.org/citations/27908889http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27908889
http://purl.uniprot.org/uniprot/P53351#attribution-A6C8B33C2A4C148C008473809C6E7065http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/27908889
http://purl.uniprot.org/uniprot/#_A0A1B0GX15-mappedCitation-27908889http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27908889
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