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• W2067707142 abstract "Transcription factors link changes in the extracellular environment with alterations in gene expression. As such, these molecules serve as attractive targets for intervention in pathological settings. Since JUN has been linked with microvascular disease in humans, we hypothesised that small interfering RNA (siRNA) targeting this immediate-early gene may be useful agents that suppress endothelial growth and neovascularisation. Here we show that Jun siRNA inhibits Jun mRNA and protein expression in murine microvascular endothelial cells, blocks cell proliferation and suppresses migration in a scratch-wound assay. It also inhibits three-dimensional tubular formation on basement membrane extracts and reduces angiogenesis in mice bearing Matrigel plugs as subcutaneous implants. Single intravitreal administration of Jun siRNA reduces neovascularisation in a murine model of proliferative retinopathy, and suppresses endothelial JUN and matrix metalloproteinase-2 (MMP-2) immunoreactivity in retinal vessels, data supported by its repression of MMP-2 expression and gelatinolytic activity in vitro. Co-administration of TGFβ with the siRNA reverses this neovascular inhibitory effect, which is in turn abrogated by cis-9-octadecenoyl-N-hydroxylamide, consistent with the involvement of a metalloproteinase such as MMP-2. Thus, JUN siRNA can serve as a specific inhibitor of aberrant endothelial and neovascular growth." @default.
• W2067707142 created "2016-06-24" @default.
• W2067707142 creator A5024904141 @default.
• W2067707142 creator A5065860849 @default.
• W2067707142 creator A5069194759 @default.
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• W2067707142 date "2006-08-01" @default.
• W2067707142 modified "2023-09-26" @default.
• W2067707142 title "JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation" @default.
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• W2067707142 doi "https://doi.org/10.1242/jcs.03059" @default.
• W2067707142 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16847049" @default.
• W2067707142 hasPublicationYear "2006" @default.
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