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http://purl.uniprot.org/citations/24177325http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24177325http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.

Approach and results

BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.

Conclusions

miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.113.302104"xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Cai J.J."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Tao J."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Wang Q."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Yuan H."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Wang J.M."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Irani K."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Chen A.F."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/author"Chen D.D."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/pages"99-109"xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/title"MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus."xsd:string
http://purl.uniprot.org/citations/24177325http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/24177325http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24177325
http://purl.uniprot.org/citations/24177325http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24177325
http://purl.uniprot.org/uniprot/Q9H2E6#attribution-8C1933BB4B6EF8A20865626D0AAA41EEhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/P29353#attribution-8C1933BB4B6EF8A20865626D0AAA41EEhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/O43597#attribution-A6648058DCFE30628F4CD6DFED95D122http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/#_D0FZQ3-mappedCitation-24177325http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/#_A2AV66-mappedCitation-24177325http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/#_P48356-mappedCitation-24177325http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24177325
http://purl.uniprot.org/uniprot/#_Q3UNU8-mappedCitation-24177325http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24177325
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