Dataset Information

[Screening of biomarkers related with leukocyte responses early after burn injury in mice by differential gene expression profiling].

ABSTRACT: OBJECTIVE:To screen the genes related with leukocyte responses in mice early after burn injury by bioinformatic analysis of the gene expression profiling data. METHODS:The gene expression profiles were obtained from GEO (GSE7404, Mouse musculus, 25% TBSA, full-thickness) database. T test, fold changes and GO functional enrichment analysis were used to identify the differentially expressed genes (DEGs) related to leukocyte responses to burns; the interacting genes were transferred to STRING to construct the protein-protein interaction (PPI) network. Biological annotation of the sub-networks was executed using the software Cytoscape. Real-time PCR and Western blotting were used to verify the DEGs in mice. RESULTS:In mice at 1 day post-burn, a total of 658 genes were up-regulated and 1167 were down-regulated. PPI network and module analysis suggested that some of the genes (Stat1, Cdk1, Cd19, Lck and Jun) may play critical roles in the PPI network post-burn. Real-time PCR and Western blotting results in mice were consistent with those of bioinformatic analysis of Stat1, Cdk1 and Jun. CONCLUSION:Stat1, Cdk1 and Jun might be critical players in the development of leukocyte response in mice early after burn injury. Our finding provides new insights into the pathogenesis of leukocyte response to burn injury and identifies several biomarkers as potential targets for burn treatment.

SUBMITTER: Zou Q

PROVIDER: S-EPMC6744150 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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[Screening of biomarkers related with leukocyte responses early after burn injury in mice by differential gene expression profiling].

Zou Qiong Q Gao Yan-Bin YB Jin Hui H Lu Zhi-Yang ZY Shi Peng-Wei PW Yang Lei L

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20170601 6

<h4>Objective</h4>To screen the genes related with leukocyte responses in mice early after burn injury by bioinformatic analysis of the gene expression profiling data.<h4>Methods</h4>The gene expression profiles were obtained from GEO (GSE7404, Mouse musculus, 25% TBSA, full-thickness) database. T test, fold changes and GO functional enrichment analysis were used to identify the differentially expressed genes (DEGs) related to leukocyte responses to burns; the interacting genes were transferred ...[more]

PMID: 28669950

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Project description:BackgroundIn the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors.MethodsWe performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05.ResultsAfter adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines.ConclusionAmong adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS.Level of evidenceEpidemiologic study, level III.

Project description:Characterization of urinary bacterial microbiome and antimicrobial peptides after burn injury to identify potential mechanisms leading to urinary tract infections and associated morbidities in burn patients.Retrospective cohort study using human urine from control and burn subjects.University research laboratory.Burn patients.None.Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from "healthy" volunteers. The urinary bacterial microbiome and antimicrobial peptide levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients versus controls, which positively correlated with a larger percent burn and with the development of urinary tract infection and sepsis postadmission, regardless of age or gender. Urinary psoriasin and ?-defensin antimicrobial peptide levels were significantly reduced in burn patients at 1 and 40 hours postadmission. We observed a shift in antimicrobial peptide hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis urinary tract infection isolates. Furthermore, the antimicrobial peptide activity in burn patients was more effective against E. coli than E. faecalis. Urinary tract infection-positive burn patients with altered urinary antimicrobial peptide activity developed either an E. faecalis or Pseudomonas aeruginosa urinary tract infection, suggesting a role for urinary antimicrobial peptides in susceptibility to select uropathogens.Our data reveal potential links for urinary tract infection development and several morbidities in burn patients through alterations in the urinary microbiome and antimicrobial peptides. Overall, this study supports the concept that early assessment of urinary antimicrobial peptide responses and the bacterial microbiome may be used to predict susceptibility to urinary tract infections and sepsis in burn patients.

Dataset Information

[Screening of biomarkers related with leukocyte responses early after burn injury in mice by differential gene expression profiling].

Publications

[Screening of biomarkers related with leukocyte responses early after burn injury in mice by differential gene expression profiling].

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