Ontology highlight
ABSTRACT:
PROVIDER: PRJNA941894 | ENA |
REPOSITORIES: ENA
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Project description:We determined which metabolic pathways are activated by hypoxia-inducible factor 1-mediated (HIF-1-mediated) protection against oxygen-induced retinopathy (OIR) in newborn mice, the experimental correlate to retinopathy of prematurity, a leading cause of infant blindness. HIF-1 coordinates the change from oxidative to glycolytic metabolism and mediates flux through serine and 1-carbon metabolism (1CM) in hypoxic and cancer cells. We used untargeted metabolite profiling in vivo to demonstrate that hypoxia mimesis activates serine/1CM. Both [13C6] glucose labeling of metabolites in ex vivo retinal explants as well as in vivo [13C3] serine labeling of metabolites followed in liver lysates strongly suggest that retinal serine is primarily derived from hepatic glycolytic carbon and not from retinal glycolytic carbon in newborn pups. In HIF-1α2lox/2lox albumin-Cre-knockout mice, reduced or near-0 levels of serine/glycine further demonstrate the hepatic origin of retinal serine. Furthermore, inhibition of 1CM by methotrexate blocked HIF-mediated protection against OIR. This demonstrated that 1CM participates in protection induced by HIF-1 stabilization. The urea cycle also dominated pathway enrichment analyses of plasma samples. The dependence of retinal serine on hepatic HIF-1 and the upregulation of the urea cycle emphasize the importance of the liver to remote protection of the retina.
2019-07-05 | MTBLS856 | MetaboLights
Project description:We determined which metabolic pathways are activated by hypoxia-inducible factor 1-mediated (HIF-1-mediated) protection against oxygen-induced retinopathy (OIR) in newborn mice, the experimental correlate to retinopathy of prematurity, a leading cause of infant blindness. HIF-1 coordinates the change from oxidative to glycolytic metabolism and mediates flux through serine and 1-carbon metabolism (1CM) in hypoxic and cancer cells. We used untargeted metabolite profiling in vivo to demonstrate that hypoxia mimesis activates serine/1CM. Both [13C6] glucose labeling of metabolites in ex vivo retinal explants as well as in vivo [13C3] serine labeling of metabolites followed in liver lysates strongly suggest that retinal serine is primarily derived from hepatic glycolytic carbon and not from retinal glycolytic carbon in newborn pups. In HIF-1?2lox/2lox albumin-Cre-knockout mice, reduced or near-0 levels of serine/glycine further demonstrate the hepatic origin of retinal serine. Furthermore, inhibition of 1CM by methotrexate blocked HIF-mediated protection against OIR. This demonstrated that 1CM participates in protection induced by HIF-1 stabilization. The urea cycle also dominated pathway enrichment analyses of plasma samples. The dependence of retinal serine on hepatic HIF-1 and the upregulation of the urea cycle emphasize the importance of the liver to remote protection of the retina.
2020-06-30 | MSV000085654 | GNPS
Project description:Phlebotomy-induced-anemia (PIA), which induces tissue hypoxia and angiogenesis, occurs universally among infants at risk for severe retinopathy of prematurity (ROP). We hypothesized that PIA exacerbates pathologic retinal neovascularization in ROP. Methods: We induced PIA to a hematocrit of 18% among rats undergoing the established 50/10 oxygen-induced retinopathy (OIR) model. Rats were euthanized at P15 and P20, during the avascular and neovascular phases of OIR, respectively. Whole retinal transcriptomes were compared to non-PIA controls. Results: RNA sequencing showed dampened pathways of angiogenesis, inflammation, and neural development in anemic OIR females at P20. Conclusion: PIA dampened transcriptomic pathways central to retinal vascular and neural development in neonatal rats. These data suggest PIA provides a protective effect from ROP.
2024-09-04 | GSE272252 | GEO
Project description:Epithelial membrane protein 2 (EMP2) regulates hypoxia induced angiogenesis in retinal epithelial cells
| PRJNA636612 | ENA
Project description:Role of microRNA-143, -150 and 126 in pathological retinal angiogenesis
| PRJNA587715 | ENA
Project description:Here we show that suppressing the serine biosynthesis pathway, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase or by exogenous serine and glycine restriction, robustly enhances polarization of interferon-g-activated macrophages (M(IFN-g)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo.To further explore its mechanism, we used high-throughput sequencing technology (RNA-seq) to assess gene expression in serine-deficiency or not BMDMs
2022-02-19 | GSE196840 | GEO
Project description:In this study, we demonstrate that SH-42 and SH-80, novel heat shock protein 90 inhibitors, suppress retinal neovascularization via inhibition of hypoxia-mediated angiogenesis. To figure out any genotoxic effect of these compounds related with heat shock protein 90 inhibition, we performed microarray analyses with retinal tissues treated with SH-42 and SH-80 for 7 days. We intravitreally injected PBS, SH42, or SH80 into the right eyes of C57BL/6 male mice (n = 12 per group). PBS-treated mice were regarded as negative control. Four retinal tissues were pooled into 1 test tube and prepared for further analyses.
2013-04-16 | E-GEOD-46057 | biostudies-arrayexpress
Project description:In this study, we demonstrate that SH-42 and SH-80, novel heat shock protein 90 inhibitors, suppress retinal neovascularization via inhibition of hypoxia-mediated angiogenesis. To figure out any genotoxic effect of these compounds related with heat shock protein 90 inhibition, we performed microarray analyses with retinal tissues treated with SH-42 and SH-80 for 7 days.
2013-04-16 | GSE46057 | GEO
Project description:Pathological retinal angiogenesis is one of the major causes of vision loss worldwide. The breakdown of blood vessels and aberrant vessels growth usually lead to hemorrhage, macular edema, fibrotic scar, and retinal detachment. OIR model serves as a proxy for human pathological retinal neovascularization such as proliferative diabetic retinopathy, retinal vein occlusion and retinopathy of prematurity. C57BL/6 mice were exposed to 75% O2 in a hyperoxic chamber from postnatal day P7 to P12 and then returned to room air. The greatest neovascular response occurred at postnatal 17 days (P17) when the mice are put back to room air condition for 5 days. In order to reveal potential genes that involve in pathological neovascularization, we performed transcriptomic analyses of retina of P17.
2024-08-20 | GSE241239 | GEO
Project description:Transcriptional mechanisms that drive angiogenesis and organotypic endothelial specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors. Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent VE-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this transcription factor. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of ß-catenin-dependent genes such as TCF/LEF1 and ZIC3 transcription factors, transporters and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 transcriptional factor gradient and enables organotypic endothelial specialization of the vascular network.
2019-12-05 | GSE141440 | GEO