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ABSTRACT:
PROVIDER: PRJNA113361 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE12011: Regulation of human endothelial gene expression by miR-126 GSE12012: Regulation of zebrafish endothelial gene expression by miR-126 Refer to individual Series
2008-08-12 | E-GEOD-12039 | biostudies-arrayexpress
Project description:Regulation of zebrafish endothelial gene expression by miR-126
| PRJNA114303 | ENA
Project description:Regulation of human endothelial gene expression by miR-126
| PRJNA114301 | ENA
Project description:Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284. Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-?). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function. Human umbilical vein endothelial cells, which express high levels of miR-126, were utilized to identify mRNA targets of miR-126. Cells were electroporated with 15 nmol of an antisense morpholino that blocks the processing of the miR-126 pri-cursor. A non-targeting morpholino (15 nmol) was used as a control. RNA was isolated 72 hr following electroporation and arrays were performed using Affymetrix Human Gene 1.0 ST arrays. Analysis was performed on three biological replicates of control morpholino and miR-126 antisense morpholino transfected cells
2008-08-12 | E-GEOD-12011 | biostudies-arrayexpress
Project description:Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284. Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function. Experiment Overall Design: To identify the genes regulated by miR-126 in vivo, flk1:GFP transgenic zebrafish embryos (which express GFP in the endothelium) were injected at the one-cell stage with 4 ng of two independent antisense morpholinos that block the processing of the miR-126 pri-cursor. At 48 hours post-fertilization, endothelial cells were isolated by fluorescence-activated cell sorting from flk1:GFP transgenic fish, and RNA was extracted. Arrays were performed on four biological replicates of control and two independent miR-126 morpholinos.
2008-10-25 | E-GEOD-12012 | biostudies-arrayexpress
Project description:Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284. Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
2008-08-12 | GSE12012 | GEO
Project description:Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284. Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
2008-08-12 | GSE12011 | GEO
Project description:The goal of this study is to investigate the cell type-specific targets of miR-126-3p in human lung microvascular endothelial cells (HLMVEC). Following the transfections of HLMVEC with non-targeting negative controls, miR-126 mimics, or miR-126 antisense inhibitors, we calculated the copy number concentration of miR-126 in each sample and performed genome-wide RNA sequencing. Plotting the gene expression data for each transfection condition (Scramble, 126-OE and 126-KD) against their respective miR-126 concentrations, we performed a linear regression analysis to discover genes that were the most sensitive to changes in miR-126 levels. We identified 1258 genes that were upregulated and 1436 genes that were downregulated by miR-126-3p. Further comparison between the downregulated genes in HLMVEC and targets predicted by online databases including TargetScan and miRDB revealed 6 genes as potential direct targets of miR-126-3p. Our study is the first to report targets of miR-126-3p in HLMVEC and demonstrate the effect of miR-126 level alteration on the HLMVEC global transcriptome. These results add to the diverse functions of miR-126-3p in different endothelial cell types and provide basis for the development of cell type-specific treatment for lung diseases.
2022-11-27 | GSE141129 | GEO
Project description:Retinal neovascularization is a severe complication of several neovascular retinal diseases, including proliferative diabetic retinopathy, central retinal vein occlusion and retinopathy of prematurity. MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. Here, we investigate the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) using miRNA-Seq. We show that miR-143-3p, miR-126-3p, and miR-150-5p are significantly downregulated in the retina of OIR rats, and intravitreal injection of synthetic mimics of these miRNAs significantly ameliorate retinal neovascularization in this animal model. Of these identified miRNAs, miR-143 which is highly expressed in the neural retina and retinal vasculature is here identified for the first time to be associated with retinal neovascularization. With a focus on miR-143 expression in primary human retinal endothelial cells, we explore its involved pathways through a multi-omics analysis. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodelling. Consequently, the multi-omics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating HIF signalling pathway. Furthermore, using cytoHubba, a topological analysis method to assess the essentiality of genes, we predict 20 top hub genes regulated by miR-143 that may be involved in mediating endothelial cell function. Using CIBERSORTx, a bulk gene expression deconvolution algorithm, we analyze a public RNA-Seq dataset (GSE102485) and demonstrate that the retinal neovascular membranes in patients with proliferative diabetic retinopathy (PDR) principally consist of endothelial cells. We then identify 2 hub genes, THBS1 and SERPINE1, direct targets of miR-143, which on further analysis demonstrate an expression level significantly altered in the PDR patients compared to controls. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization. The present study might have important implications for the exploration of potential therapeutic targets for the treatment of neovascular ocular diseases.
2026-06-29 | PXD029706 | Pride
Project description:microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
2013-11-24 | GSE51255 | GEO