Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1115224 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:As an endothelium destabilizer, CD82 facilitates vascular leakage by disrupting endothelial barrier and inhibiting its recovery during inflammation. AC at EC surface primes and promotes vascular leakage, mediates the effect of CD82 or TEMD on inflammation, and can be regulated specifically by i) tetraspanins or TEMDs, ii) ORP-mediated transfer of cholesterol, iii) environmental cholesterol, and iv) statin. Thus, tetraspanin-AC interaction and subcellular cholesterol compartmentalization tune the balances between antagonistic signaling axes of Cdc42 versus RhoA, to alter vascular leakage in inflammation. Equally important, we demonstrated anti-vascular leakage and anti-inflammation roles of i) AC reduction and ii) FARP1-Cdc42 elevation/activation in animal models, with promising translational and clinical prospects.
2025-06-19 | PXD065001 | Pride
Project description:The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER . Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in tissue cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.
2024-01-11 | GSE250230 | GEO
Project description:We report the chromatin accessibility of rat vascular smooth muscle cell at de-differentiated state (induced by DAPT treatment), inflammatory state (induced by cholesterol treatment) and macrophage-like state (induced by combined treatment of DAPT and cholesterol)
2025-05-29 | GSE216071 | GEO
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146108 | GEO
Project description:Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
2020-04-06 | GSE146107 | GEO
Project description:Pathological increases in vascular permeability lead to edema and swelling, causing a host of retinal and neurological disorders. Few barrier-enhancing factors have been discovered to specifically promote barrier integrity and make blood vessels resistant to fluid leakage. In this study, we explore the effects of IL-36 receptor (IL-36R) activation on vascular permeability in vivo in adult mice, ex vivo in tissue explant and in vitro in primary mouse and human microvascular endothelial cells. Using a highly soluble and biologically active DEVD- modified recombinant IL-36β cytokine, we find that processed DEVDIL-36β enhances endothelial barrier function, reducing vascular leakage and thus limiting pathology. Specific knockdown of IL-36R on endothelial cells using the Cre/Lox system demonstrates it is IL-36R signaling in endothelial cells that is responsible for DEVDIL-36β’s barrier-promoting property. Analysis of IL-36R expression and localization on endothelial cells implies IL-36R is mobilized to the plasma membrane in response to loss of endothelial cell-cell contact, in keeping with the IL-1 family role in responding to tissue stress. Mechanistically, IL-36R signaling increases adherens and tight junctions and induces vasculoprotective processes that result in vessel remodeling and stabilization. These functional assays are further supported by RNA sequencing data. In summary, our data present IL-36R signaling as a novel regulator of vascular integrity, with barrier-enhancing properties that prevent pathological vascular leakage.
2025-11-15 | GSE307365 | GEO
Project description:Accessible cholesterol, the pool of membrane cholesterol with high chemical activity, regulates vital processes including vertebrate development and pathogen evasion. The mechanisms that govern plasma membrane (PM) cholesterol accessibility are incompletely understood. Using a genome-wide screen we find that acetyl-CoA carboxylase alpha (ACC1) loss causes a ~10-fold increase in PM accessible cholesterol in cells and a male mouse model. We demonstrate that reduced fatty acyl-CoA levels, achieved by targeting metabolic enzymes including ACC1, fatty acid synthase (FASN) or acyl-CoA synthetases long chain (ACSL1, 3 and 4), results in the activation of adipose triacylglycerol lipase (ATGL). ATGL activation elevates the abundance of polyunsaturated diacylglycerols through a mechanism that is independent of triacylglycerol hydrolysis. These diacylglycerol species are utilized to generate polyunsaturated phosphatidylcholine and phosphatidylethanolamine, which raises PM fluidity and cholesterol accessibility. Conversely, ATGL inhibition rigidifies the PM, reducing PM accessible cholesterol. Increased PM fluidity impairs cholesterol transport, triggering SREBP2 activation. This study reveals a surprising link between fatty acid metabolism and cholesterol homeostasis, demonstrating that ATGL can modify the lipidome through a triacylglycerol-independent mechanism.
2026-09-18 | GSE346963 | GEO
Project description:Hypercholesterolemia has long been implicated in endothelial cell (EC) dysfunction, but the mechanisms by which excess cholesterol causes vascular pathology are incompletely understood. Here we used a cholesterol-mimetic probe to map cholesterol-protein interactions in primary human ECs and discovered that cholesterol binds to and stabilizes the adhesion molecule VCAM-1. We show that accessible plasma membrane (PM) cholesterol in ECs is acutely responsive to inflammatory stimuli and that the nonvesicular cholesterol transporter Aster-A regulates VCAM-1 stability in activated ECs by controlling the size of this pool. Deletion of Aster-A in ECs increases VCAM-1 protein, promotes immune cell recruitment to vessels, and impairs pulmonary immune homeostasis. Conversely, depleting cholesterol from the endothelium in vivo dampens VCAM-1 induction in response to inflammatory stimuli. These findings identify cholesterol binding to VCAM-1 as a key step during EC activation and provide a biochemical explanation for the ability of excess membrane cholesterol to promote immune cell recruitment to the endothelium.
| MSV000099325 | MassIVE
Project description:Fatty acid metabolism controls plasma membrane cholesterol accessibility via ATGL-dependent phospholipid remodeling
| PRJNA1527384 | ENA