Effect of LPS treatment on gene expression in the murine adrenal cortex
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ABSTRACT:
PROVIDER: PRJNA823703 | ENA |
REPOSITORIES: ENA
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Project description:Although of the utmost importance for our survival, the activation of the adrenal gland is often impaired during sepsis. Little is known about the mechanisms involved in this process. In the present study, we have used a robust RNA Sequencing (RNA-Seq) technology in a search for novel transcriptomic signatures in adrenal glands triggered by bacterial lipopolysaccharide-induced systemic inflammation. Our results demonstrate that LPS injection to mice induce a robust change in the adrenal transcriptome, significantly altering the expression of 8458 genes as compared to saline injected animals. The principal component analysis shows a clear separation between LPS and saline treatments, as well as show low variance between biological samples from each group. The functional analysis of 4312 upregulated and 4146 downregulated genes by LPS, demonstrate a strong induction of genes involved in inflammatory and steroidogenic responses, and inhibition of genes involved in DNA repair and stem/progenitor cell pathways. Gene enrichment set analysis (GSEA) further validated the functional data, and indicated a strong grouping of genes involved in LPS-mediated induction of interferon and innate immune responses, along with previously unexplored activation of the hypoxia and inhibition of Wnt/Shh pathways in the adrenal gland. These results were further validated by quantitative PCR analysis. Collectively, this is the first study demonstrating a global alteration of adrenal gene signatures during systemic inflammation, indicating the potential pathways that are involved in the adrenal gland dysregulation during sepsis.
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