Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

ABSTRACT: The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes. Though sustained hyper-O-GlcNAcylation aggravates pathogenesis of many chronic diseases, accumulating evidence also indicates that acute augmentation in O-GlcNAcylation seems to benefit disease healing in some cases. Glucosamine (GlcN) is a freely available and commonly used dietary supplement for human cartilage health, which also activates the hexosamine biosynthesis pathway and induces protein O-GlcNAcylation. Here we show that both GlcN early and late therapies effectively facilitate cardiac recovery in mice by elevating accumulation of Ly6Clow Mo/Mps in infarcted hearts. Eliminating Mo/Mps with clodronate liposomes fully abolishes aforementioned cardiac healing role of GlcN. Importantly, GlcN supplementation accelerates not only in vitro mobility of reparative Mo/Mps but also in vivo infiltration of Ly6Clow Mos. Mechanistically, GlcN positively regulates transcription of myeloid CX3C chemokine receptor 1 (Cx3cr1) by improving STAT1 O-GlcNAcylation, which stabilizes STAT1 and subsequently promotes chemotaxis and infiltration of Ly6Clow Mos. In summary, we identify a novel anti-inflammatory role of GlcN and suggest that its protective effects are mediated through chemotaxis of Ly6Clow Mos in a STAT1/CX3CR1-dependent fashion, which is controlled by O-GlcNAcylation of STAT1. Our study provides a novel clue for Mo/Mps modulator therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.

ORGANISM(S): Mus musculus

PROVIDER: GSE193613 | GEO | 2022/04/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Perilipin 2-positive mononuclear phagocytes accumulate in diabetic retina and promote PPARγ-dependent vasodegeneration

Project description:Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia leads to non-proliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retinal barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas express PLIN2, a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from T2DM patients or with palmitate concentrations typical of T2DM plasma, but not under high glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induce capillary degeneration in ex vivo explants, which was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study provides a novel mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target to inhibit lipid-activated MPs in DR

2023-08-31 | GSE239512 | GEO

Inflammation switches the differentiation program of Ly6Chi monocytes from anti-inflammatory macrophages to inflammatory dendritic cells in the colon

Project description:Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hi CX3CR1hi (CD11b+CD103-) cells account for 80% of mouse colonic lamina propria (cLP) MHC-IIhi cells. Both CD11c+ and CD11c- cells within this population were identified as MPs based on multiple criteria, including a MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs, based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+ DCs and CD103-CX3CR1intCD11b+ DCs. In non-inflammatory conditions, Ly6Chi monocytes differentiated primarily into CD11c+, but not CD11c- MPs. In contrast, during colitis, Ly6Chi monocytes massively invaded the colon and differentiated into pro-inflammatory CD103-CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS and TNF. These findings demonstrate the dual capacity of Ly6Chi blood monocytes to differentiate into either regulatory MPs or inflammatory DCs in the colon, and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions. FACS sorted expression from normal controls

2011-12-21 | E-GEOD-27859 | biostudies-arrayexpress

Triggering of NOD2 receptor converts inflammatory Ly6Chigh into Ly6Clow monocytes with patrolling properties.

Project description:In the present study, we demonstrate that NOD2 receptor triggering by muramyl dipeptide converts blood inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Muramyl dipeptide administration to Nr4a1-/- mice, which lack Ly6Clow monocytes, and to Ly6Clow-depleted mice leads to the emergence of blood patrolling monocytes expressing phenotypic profile of typical Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Furthermore using intravital microscopy in live animal models of inflammatory diseases, we observed that converted Ly6Chigh monocytes are capable of patrolling the endothelium of blood vessels and their presence contributes to reduce the inflammatory response following muramyl dipeptide injection.

2019-01-14 | GSE101496 | GEO

Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

Project description:Glucosamine facilitates cardiac ischemic recovery via recruiting Ly6Clow monocytes in a STAT1 O-GlcNAcylation dependent fashion

| PRJNA796947 | ENA

Cx3cr1-deficient microglia exhibit a premature aging transcriptome

2019-11-25 | GSE131869 | GEO

Retinal Ly6Clow Mo/MΦ protect optic nerve against injury

Project description:We investigate the therapeutic effect of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs), a potent immune-modulating therapy for tissue regeneration, in repairing optic nerve damage. Intraocular administration of MSC-sEVs promotes both RGC survival and axon regeneration against optic nerve crush injury. Mechanistically, MSC-sEVs recruits a neural restorative population of hematogenous Ly6Clow monocyte/monocyte-derived macrophage (Mo/MΦ). Gain-of-function by intravitreal administration of the donor Ly6Clow Mo/MΦ markedly improves neurological outcomes in vivo. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.

2024-02-21 | GSE223529 | GEO

Inflammation switches the differentiation program of Ly6Chi monocytes from anti-inflammatory macrophages to inflammatory dendritic cells in the colon

2011-12-21 | GSE27859 | GEO

Cx3cr1-deficient microglia exhibit a premature aging transcriptome

Project description:CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-Seq. In 2 mos mice, Cx3cr1 deletion resulted in the downregulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a compatible fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.

2019-10-01 | GSE130960 | GEO

Retinal Ly6Clow Mo/MΦ protect optic nerve against injury

Project description:Retinal Ly6Clow Mo/MΦ protect optic nerve against injury

| PRJNA926649 | ENA

MSC-sEV regulates Ly6Clow Mo/MΦ in neural restoration

Project description:MSC-sEV regulates Ly6Clow Mo/MΦ in neural restoration

| PRJNA929506 | ENA