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http://purl.uniprot.org/citations/24844779http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24844779http://www.w3.org/2000/01/rdf-schema#comment"

Aims

Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression.

Results

We found that hypoxia induced miR-101, which binds to the 3'untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow.

Innovation

Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir.

Conclusion

Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.org/dc/terms/identifier"doi:10.1089/ars.2014.5856"xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Kim J.H."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Kim J."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Lee H."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Lee K.S."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Choe J."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Kim Y.M."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Ha K.S."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Lee D.K."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Won M.H."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Jeoung D."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Kwon Y.G."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Kwak S.N."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/author"Cho B.R."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/name"Antioxid Redox Signal"xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/pages"2469-2482"xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/title"Hypoxia-responsive microRNA-101 promotes angiogenesis via heme oxygenase-1/vascular endothelial growth factor axis by targeting cullin 3."xsd:string
http://purl.uniprot.org/citations/24844779http://purl.uniprot.org/core/volume"21"xsd:string
http://purl.uniprot.org/citations/24844779http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24844779
http://purl.uniprot.org/citations/24844779http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24844779
http://purl.uniprot.org/uniprot/Q13618#attribution-63B5E53B6267F984167E27D2CE8FBDB3http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24844779
http://purl.uniprot.org/uniprot/P09601#attribution-63B5E53B6267F984167E27D2CE8FBDB3http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24844779
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