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Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization

ABSTRACT: Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization

PROVIDER: PRJNA912646 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22750362_1.fastq.gz	Fastqsanger.gz
	SRR22750362_2.fastq.gz	Fastqsanger.gz
	SRR22750363_1.fastq.gz	Fastqsanger.gz
	SRR22750363_2.fastq.gz	Fastqsanger.gz
	SRR22750364_1.fastq.gz	Fastqsanger.gz

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Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization

Project description:Background: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. Results: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells. We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. WT1-AS, LINC01140, and LUCAT1 were situated at the center of the network. Additionally, several key angiogenic genes, such as apelin, angiomotin, and C-X-C motif chemokine ligand 10, were found to potentionally interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. Conclusions: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.

2023-06-21 | GSE221037 | GEO

A local neuronal clock regulates retinal angiogenesis and neovascularization

Project description:Emerging evidence suggests a link between the circadian clock and retinopathies though the causality has not been established. Circadian clocks in the mammalian retina regulate a diverse range of retinal functions that allow the retina to adapt to the light-dark cycle. We report that clock genes are expressed in the embryonic retina, and the embryonic retina requires light cues to maintain robust circadian expression of the core clock gene, Bmal1. Deletion of Bmal1 and Per2 from the retinal neurons results in retinal angiogenic defects similar to when animals are maintained under constant light conditions. Using two different models to assess pathological neovascularization, we show that neuronal Bmal1 deletion reduces neovascularization with reduced vascular leakage, suggesting that a dysregulated circadian clock primarily drives neovascularization. Chromatin immunoprecipitation sequencing analysis suggests that semaphorin signaling is the dominant pathway regulated by Bmal1. Our data indicate that therapeutic silencing of the retinal clock could be a common approach for the treatment of certain retinopathies like diabetic retinopathy and retinopathy of prematurity.

2022-07-01 | GSE207271 | GEO

Genetic targeting or pharmacological inhibition of galectin-3 dampens microglia reactivity and delays retinal degeneration

Project description:Dysfunctional humoral and cellular innate immunity are key components in the development and progression of age-related macular degeneration (AMD). Specifically, chronically activated microglia and their disturbed regulatory system contribute to retinal degeneration. Galectin-3, a b-galactose binding protein, is a potent driver of macrophage and microglia activation and has been implicated in neuroinflammation, including neurodegenerative diseases of the brain. Here, we report that galectin-3 is strongly upregulated in reactive retinal microglia of AMD patients and in two related mouse models of retinal degeneration. Specific targeting of galectin-3 by genetic knockout or using the small-molecule inhibitor TD139 blocks microglia reactivity and protects from retinal damage in different models of light-induced retinal degeneration. These data define galectin-3 as potent driver of retinal degeneration and highlight the protein as a drug target for ocular immunomodulatory therapies.

2022-08-15 | GSE211119 | GEO

Monocyte histone lactylation-regulated exosomal periostin promotes retinal neovascularization

Project description:Exosomes serve as signaling messengers that facilitate intercellular communication through delivering molecular cargo. Here, we observed elevated levels of exosomal periostin (POSTN) in blood plasma of patients with proliferative diabetic retinopathy (PDR). Monocytes-derived exosomal POSTN was increased under high glucose condition, and deletion of Postn in myeloid cells reduced retinal neovascularization. Monocytes isolated from the blood of PDR patients exhibited heightened glycolytic activity and elevated histone lactylation levels, particularly H4K8 lactylation (H4K8la). Knockout of Hexokinase 2 (Hk2) in myeloid cells led to reduced H4K8la and POSTN levels and inhibited retinal neovascularization. Exogenous exosomal POSTN partially reversed the angiogenic defects caused by Postn or Hk2 deletion in myeloid cells. Mechanistically, exosomal POSTN stabilized hypoxia-inducible factor 1-alpha (HIF1-α) and upregulated the expression of angiogenic genes. Notably, treatment with metformin reduced retinal neovascularization by decreasing monocytes glycolysis and lowering exosomal POSTN levels. In summary, these findings underscore the critical role of circulating exosomal POSTN in retinal neovascularization and highlight its potential as a therapeutic target for angiogenic retinopathies.

2025-01-20 | PXD059956 |

Transcriptional Comparison of Human and Murine Retinal Neovascularization

Project description:Transcriptional Comparison of Human and Murine Retinal Neovascularization

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A local neuronal clock regulates retinal angiogenesis and neovascularization

Project description:A local neuronal clock regulates retinal angiogenesis and neovascularization

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Gene Expression Profiling In Murine Retina Neovascularization Models

Project description:In order to find out the vital genes during retinal neovascularization (RNV), we set up OIR (oxygen-induced retinopathy; induced with 75%Â±2% oxygen) and wild-type C57BL/6J murine models. We observed the retinal vascular growth process daily both in OIR and wild-type mice through retinal flat-mount, and isolated total retinal RNA at different time points (P8, P9, P12, P13, P30) both in OIR and wild-type mice for gene expression analysis. At least three different retinae were accessed at each time point for observing the retinal vascular growth process. Ten neural retinae from five mice were harvested and pooled into one sample for gene expression analysis. Three biological replicates were used for each time point. Dye-swaps were performed.

2012-12-05 | E-GEOD-38762 | biostudies-arrayexpress

Expression profiling of microRNAs in oxygen-induced retinal neovascularization in mice

Project description:The purpose of this study is to identify disease-related miRNAs in retinas of a mouse model of oxygen-induced retinopathy (OIR). OIR pups were exposed to 75% oxygen at postnatal day (P)7 for 5 days, and were returned to room air at P12. The miRNAs expression profiles in the retinas from OIR mice at P17 and room air controls were determined through microarray analysis. Expressions of significantly upregulated and downregulated miRNAs in the OIR retinas and controls were confirmed through quantitative real-time RT-PCR (qPCR). Compared to the room air controls, 3 miRNAs were significantly up-regulated, and 8 miRNAs were down-regulated in OIR retinas. Our findings indicated that several miRNAs were differentially expressed in the oxygen-induced retinal neovascularization, which might provide novel therapeutic targets in regulating retinal neovascular diseases.

2018-06-19 | GSE115949 | GEO

Gene Expression Profiling In Murine Retina Neovascularization Models

Project description:In order to find out the vital genes during retinal neovascularization (RNV), we set up OIR (oxygen-induced retinopathy; induced with 75%±2% oxygen) and wild-type C57BL/6J murine models. We observed the retinal vascular growth process daily both in OIR and wild-type mice through retinal flat-mount, and isolated total retinal RNA at different time points (P8, P9, P12, P13, P30) both in OIR and wild-type mice for gene expression analysis.

2012-12-05 | GSE38762 | GEO

Expression profiling of microRNAs in oxygen-induced retinal neovascularization in mice

Project description:Expression profiling of microRNAs in oxygen-induced retinal neovascularization in mice

| PRJNA476577 | ENA