Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression.
15-lipoxygenase-1 (15-LOX-1) plays an important role in angiogenesis, but how it works still remains a controversial subject. The aims of our study are focused on determining whether or not 15-LOX-1 inhibiting oxygen-induced ischemic retinal neovascularization (RNV) and the underlying regulatory mec...
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| Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3897531?pdf=render |
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| author | Zhi Li Tao He Ke Du Yi-Qiao Xing Yuan-Min Run Ying Yan Yin Shen |
| author_facet | Zhi Li Tao He Ke Du Yi-Qiao Xing Yuan-Min Run Ying Yan Yin Shen |
| author_sort | Zhi Li |
| collection | DOAJ |
| description | 15-lipoxygenase-1 (15-LOX-1) plays an important role in angiogenesis, but how it works still remains a controversial subject. The aims of our study are focused on determining whether or not 15-LOX-1 inhibiting oxygen-induced ischemic retinal neovascularization (RNV) and the underlying regulatory mechanism involving of 15-LOX-1, peroxisome proliferator-activated receptor γ (PPAR-γ) and vascular endothelial growth factor receptor 2 (VEGFR-2) in oxygen-induced retinopathy (OIR). Recombinant adenoviral vectors that expressing the 15-LOX-1 gene (Ad-15-LOX-1-GFP) or the green fluorescence protein gene (Ad-GFP) were intravitreous injected into the OIR mice at postnatal day 12 (P12), the mice were sacrificed 5 days later (P17). Retinal 15-LOX-1 expression was significantly increased at both mRNA and protein levels after 15-LOX-1 gene transfer. Immunofluorescence staining of retinal sections revealed 15-LOX-1 expression was primarily in the outer plexiform layer (OPL), inner nuclear layer (INL) and ganglion cell layer (GCL) retina. Meanwhile, RNV was significantly inhibited indicated by fluorescein retinal angiography and quantification of the pre-retinal neovascular cells. The expression levels of PPAR-γ were significantly up-regulated while VEGFR-2 were significantly down-regulated both in mRNA and protein levels. Our results suggested 15-LOX-1 gene transfer inhibited RNV in OIR mouse model via up-regulation of PPAR-γ and further down-regulation of VEGFR-2 expression. This could be a potentially important regulatory mechanism involving 15-LOX-1, PPAR-γ and VEGFR-2 during RNV in OIR. In conclusion, 15-LOX-1 may be a new therapeutic target for treating neovascularization diseases. |
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| language | English |
| last_indexed | 2024-12-14T00:48:55Z |
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| spelling | doaj.art-683d106c34e745c1af276ebd4ad288d22022-12-21T23:23:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8582410.1371/journal.pone.0085824Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression.Zhi LiTao HeKe DuYi-Qiao XingYuan-Min RunYing YanYin Shen15-lipoxygenase-1 (15-LOX-1) plays an important role in angiogenesis, but how it works still remains a controversial subject. The aims of our study are focused on determining whether or not 15-LOX-1 inhibiting oxygen-induced ischemic retinal neovascularization (RNV) and the underlying regulatory mechanism involving of 15-LOX-1, peroxisome proliferator-activated receptor γ (PPAR-γ) and vascular endothelial growth factor receptor 2 (VEGFR-2) in oxygen-induced retinopathy (OIR). Recombinant adenoviral vectors that expressing the 15-LOX-1 gene (Ad-15-LOX-1-GFP) or the green fluorescence protein gene (Ad-GFP) were intravitreous injected into the OIR mice at postnatal day 12 (P12), the mice were sacrificed 5 days later (P17). Retinal 15-LOX-1 expression was significantly increased at both mRNA and protein levels after 15-LOX-1 gene transfer. Immunofluorescence staining of retinal sections revealed 15-LOX-1 expression was primarily in the outer plexiform layer (OPL), inner nuclear layer (INL) and ganglion cell layer (GCL) retina. Meanwhile, RNV was significantly inhibited indicated by fluorescein retinal angiography and quantification of the pre-retinal neovascular cells. The expression levels of PPAR-γ were significantly up-regulated while VEGFR-2 were significantly down-regulated both in mRNA and protein levels. Our results suggested 15-LOX-1 gene transfer inhibited RNV in OIR mouse model via up-regulation of PPAR-γ and further down-regulation of VEGFR-2 expression. This could be a potentially important regulatory mechanism involving 15-LOX-1, PPAR-γ and VEGFR-2 during RNV in OIR. In conclusion, 15-LOX-1 may be a new therapeutic target for treating neovascularization diseases.http://europepmc.org/articles/PMC3897531?pdf=render |
| spellingShingle | Zhi Li Tao He Ke Du Yi-Qiao Xing Yuan-Min Run Ying Yan Yin Shen Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. PLoS ONE |
| title | Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. |
| title_full | Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. |
| title_fullStr | Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. |
| title_full_unstemmed | Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. |
| title_short | Inhibition of oxygen-induced ischemic retinal neovascularization with adenoviral 15-lipoxygenase-1 gene transfer via up-regulation of PPAR-γ and down-regulation of VEGFR-2 expression. |
| title_sort | inhibition of oxygen induced ischemic retinal neovascularization with adenoviral 15 lipoxygenase 1 gene transfer via up regulation of ppar γ and down regulation of vegfr 2 expression |
| url | http://europepmc.org/articles/PMC3897531?pdf=render |
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