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Series GSE225236 Query DataSets for GSE225236
Status Public on May 05, 2023
Title Shock drives a highly coordinated transcriptional and DNA methylation response in the endothelium
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Endothelial dysfunction is a critical factor in promoting organ failure during septic shock. Organ dysfunction during shock increases the risk of long-term sequelae in survivors through mechanisms that remain unknown. We postulated that vascular dysfunction during shock contributes to long-term morbidity post-shock through transcriptional and epigenetic changes within the endothelium. We performed cross-omics analyses on kidney endothelium from acute endotoxin-challenged mice lacking or not the JAK/STAT3 inhibitor SOCS3. This analysis revealed significant DNA methylation changes upon proinflammatory signaling associated with transcriptional activity through AP1, STAT, and IRF families, suggesting a mechanism driving transcription-induced gene-specific methylation changes. In vitro, we demonstrated that IL-6 induces similar changes in DNA methylation. Specific genes showed DNA methylation changes in response to an IL-6+R and consistently changes in their expression levels within 72 hours of IL-6+R treatment. Further, changes in the endothelial methylome remain in place for prolonged periods without IL-6, suggesting that this cytokine may elicit transcriptional changes long after the resolution of inflammation. Also, demonstrated that DNA methylation changes could directly alter the expression of these genes and that STAT3 activation had a causal role in this transcriptional response. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for HUVEC cells treated with a combination of IL-6+R or saline for 72h prior to the RNA-seq.
 
Contributor(s) Bossardi Ramos R, Adam AP
Citation(s) 37667913
Submission date Feb 13, 2023
Last update date Sep 12, 2023
Contact name Ramon Bossardi Ramos
E-mail(s) bossarr@amc.edu
Organization name Albany Medical College
Department Department of Molecular and Cellular Physiology
Lab Adam's Lab
Street address 43 New Scotland Avenue
City Albany
State/province Ny
ZIP/Postal code 12208
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (8)
GSM7042319 HUVEC, IL6 72h - 1
GSM7042320 HUVEC, IL6 72h - 2
GSM7042321 HUVEC, IL6 72h - 3
Relations
BioProject PRJNA934391

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE225236_counts_per_sample.csv.gz 539.1 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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