Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing
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PROVIDER: PRJNA443000 | ENA |
REPOSITORIES: ENA
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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
Project description: Not available
| S-EPMC6413785 | biostudies-literature
Project description: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.
2023-06-01 | GSE233629 | GEO
Project description:Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized. We used data from microarrays to (1) determine the effects of phosphate restriction on the biologic functions identified from the gene expression in fracture calluses; and (2) examine whether there are genetic differences within the primary biologic functions.
2018-12-25 | GSE99580 | GEO
Project description:The aim of this study was to identify the genes differentially expressed between timepoints in the week following tympanic membrane perforation in rats. Tissue from 240 individual rats was used in this study following random allocation into timepoint groups to be sacrificed over 7 days. An Agilent one color microarray technique was performed and the results were analyzed using Genespring GX9 software. A total of 3262 genes were identified as significant (p<0.05) and differentially expressed above a two-fold threshold between the timepoints. This study provides a complete genetic review of rat tympanic membrane wound healing over 7 days. The results can be used as a model for other wound healing in other mammals and in different parts of the body. The information on differential gene expression can be used in research towards developing chronic tympanic membrane perforations and also in research to treat acute and chronic tympanic membrane perforations. The microarray was performed on animals in a disease free environment and the genetic information can be compared to future research in disease states of the TM including Otitis media, cholesteatoma, chronic perforation and tympanosclerosis. Rats were randomly selected as either controls or in the perforation group. Perforations were created unilaterally (left ear) in the upper outer quadrant of the pars tensa of ratsâ tympanic membranes using sterile 23 gauge needles . Rats were then randomly allocated into timepoint groups to be sacrificed at either 12, 24, 36, day 2, 3, 4, 5, 6, 7. At the point of microarray, there were 18 rats per timepoint group and 18 controls.
2010-08-18 | E-GEOD-17698 | biostudies-arrayexpress
Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
2020-04-25 | GSE149314 | GEO
Project description:The aim of this study was to identify the genes differentially expressed between timepoints in the week following tympanic membrane perforation in rats. Tissue from 240 individual rats was used in this study following random allocation into timepoint groups to be sacrificed over 7 days. An Agilent one color microarray technique was performed and the results were analyzed using Genespring GX9 software. A total of 3262 genes were identified as significant (p<0.05) and differentially expressed above a two-fold threshold between the timepoints. This study provides a complete genetic review of rat tympanic membrane wound healing over 7 days. The results can be used as a model for other wound healing in other mammals and in different parts of the body. The information on differential gene expression can be used in research towards developing chronic tympanic membrane perforations and also in research to treat acute and chronic tympanic membrane perforations. The microarray was performed on animals in a disease free environment and the genetic information can be compared to future research in disease states of the TM including Otitis media, cholesteatoma, chronic perforation and tympanosclerosis.
2009-08-19 | GSE17698 | GEO
Project description:In order to clarify the human response of re-epithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. Altogether 25 biopsies from 8 patients qualified for the study. All samples were analysed by genome-wide microarrays. Here we identified the genes associated with normal skin re-epithelialization on time-scale, and organized them by similarities according to their induction or suppression patterns during wound healing. Overall 25 samples were analyzed
2011-04-29 | E-GEOD-28914 | biostudies-arrayexpress
Project description:S.ciliatum wound healing - transcriptome sequencing
| PRJEB49227 | ENA