Transcriptomic profiling of LPS-induced adrenal inflammation in WT mice

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. Examination of acute LPS-induced transcriptomic changes in mouse adrenal gland

尽管肾上腺激活对机体生存至关重要，但脓毒症（sepsis）过程中其功能常受到损害。目前对于该过程的潜在分子机制仍有待阐明。
本研究采用性能优异的RNA测序（RNA Sequencing, RNA-Seq）技术，旨在探寻细菌脂多糖诱导的全身性炎症所触发的肾上腺转录组新特征。研究结果显示，向小鼠注射脂多糖（LPS）可引发肾上腺转录组的显著变化：与注射生理盐水的对照组小鼠相比，LPS处理组显著改变了8458个基因的表达水平。主成分分析（Principal Component Analysis, PCA）结果表明，LPS处理组与生理盐水对照组呈现清晰的分离趋势，且每组内的生物学样本间方差较低。
对LPS处理后上调的4312个基因与下调的4146个基因进行功能分析，结果显示：参与炎症反应与类固醇生成应答的基因被显著诱导，而参与DNA修复以及干细胞/祖细胞通路的基因则受到抑制。基因集富集分析（Gene Set Enrichment Analysis, GSEA）进一步验证了上述功能分析结果，表明参与LPS介导的干扰素与固有免疫应答的基因呈现显著聚集，同时还发现了此前未被报道的肾上腺组织中缺氧通路激活与Wnt/Shh通路抑制现象。
上述结果通过实时定量聚合酶链式反应（quantitative PCR, qPCR）分析得到了进一步验证。
综上，本研究首次揭示了全身性炎症过程中肾上腺基因表达特征的全局性改变，明确了脓毒症过程中肾上腺功能失调所涉及的潜在通路。
小鼠肾上腺急性LPS诱导转录组变化的研究