Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation

ABSTRACT: Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.

ORGANISM(S): Mus musculus

PROVIDER: GSE233629 | GEO | 2023/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing

Project description:We generated a genomic and phenotypic resource comprising genetically outbred mice in which we measured (i) quantitative differences in wound healing indicated as ear area (ii) bone marrow derived macrophage (BMDM) mRNA expression by RNA-sequencing (RNA-seq), (iii) genome-wide SNPs genotyping by low-coverage sequencing.We performed gene co-expression network analysis and we identified a network in macrophages enriched in cholesterol genes which is genetically controlled by Runx2 gene. In vivo pharmacological blockage of Fasn with cerulenin showed delayed wound healing in rats and increased macrophage recruitment to the wound.

2019-01-11 | GSE112171 | GEO

TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ChIP-seq]

Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.

2019-04-03 | GSE129202 | GEO

TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ATAC-seq]

2019-04-03 | GSE129167 | GEO

TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [RNA-seq]

2019-04-03 | GSE129210 | GEO

TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [scRNA-seq]

2019-04-03 | GSE129225 | GEO

Transcription profiling of wounds from ovariectomized MIF null mice and controls to investigate the role of MIF during wound healing using BALB/C MIF null mice

Project description:The aim of this experiment was to investigate the role of MIF during wound healing using BALB/C MIF null mice and in the context of reduced estrogen-associated impaired healing using ovariectomized mice (a mouse model of age-associated delayed healing). Ageing is associated with delayed cutaneous wound healing resulting from reduced estrogen levels. Macrophage migration inhibitory factor (MIF - NCBI RefSeq: NM_010798) is thought to mediate the effects of estrogen on wound healing. Gene expression was compared between wounds from ovariectomized MIF null mice and controls.

2005-11-05 | E-MEXP-209 | biostudies-arrayexpress

Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing

Project description:Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing

| PRJNA443000 | ENA

Neutrophil Extracellular Traps (NETs) promote macrophage inflammation and impair atherosclerosis resolution in mice with diabetes

Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. In diabetes they are increased and impair wound healing, during which inflammation normally resolves. Atherosclerosis regression, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis regression in diabetes through unresolved inflammation. Objective: To investigate in diabetes the effect of NETs on plaque macrophage inflammation and whether NETs reduction improves atherosclerosis regression. Findings: Transcriptomic profiling of plaque macrophages from NET positive and negative areas in Ldlr-/- mice revealed inflammasome and glycolysis pathway upregulation, indicating a pro-inflammatory phenotype. During atherosclerosis regression in non-diabetic mice, plaque NET content decreased. In contrast, in diabetic mouse plaques NETs were enriched and persisted after lipid-lowering. DNase1 treatment (to degrade NETs) of diabetic mice reduced plaque NETs and macrophage inflammation and improved atherosclerosis regression after lipid-lowering. Conclusions: NETs decline during atherosclerosis regression in non-diabetic mice, but persist in diabetes and impair regression by exacerbating macrophage inflammation. DNase1 reduced diabetic plaque NETs and macrophage inflammation, and restored atherosclerosis resolution after lipid-lowering, despite ongoing hyperglycemia. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid-lowering, these data suggest that NETs contribute to the increased CVD risk in this population.

2020-05-12 | GSE145200 | GEO

HDL suppresses the type I interferon response

Project description:Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDL’s ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathway’s potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDL’s major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-I–deficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection. 12 arrays, 3 experimental groups, mMncN (no treatment), mMncL (LPS treated, exposed for 4 h to serum-free medium or serum-free medium supplemented with 100 ng/mL of LPS), and mMwtL (HDL treated, Macrophages were treated for 4 h with serum-free medium or serum-free medium supplemented with 50 mg/mL of HDL, washed twice with PBS).

2010-10-01 | E-GEOD-19340 | biostudies-arrayexpress

ANKRD1 promotes cell migration by suppressing ELN production during early senescence

Project description:Cellular senescence is a complex biological process that contributes to wound healing, carcinogenesis, and age-related disease. Although the molecular mechanisms whereby senescence promotes wound repair are not well understood, the protein ANKRD1, which promoted wound healing in mice, was found to increase in senescent cells. We hypothesized that ANKRD1 may play a role in senescence-mediated wound healing. Conditioned medium (CM) from senescent WI-38 human diploid fibroblasts hastened cell migration of human HaCaT keratinocytes. Interestingly, silencing ANKRD1 in WI-38 cells reduced the effect of CM on cell migration, while overexpressing ANKRD1 accelerated it. Further proteomic analysis revealed that ANKRD1 associates with YBOX1, a multifunctional protein that modulates transcription of the ELN gene and reduces ELN mRNA production. The product of the ELN gene, the protein ELN or tropoelastin (a subunit of elastin), is a secreted factor that reduces motility. Thus, we propose that a rise in ANKRD1 during early senescence transiently limits the YBOX1-dependent transcriptional increase in ELN production, and thereby enables cell motility in early phases of senescence.

2023-06-01 | MSV000092079 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data