The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.
The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs.
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DOI：
10.1371/journal.pone.0093846
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sullivan KE
中科院分区：
文献类型：
--
作者：
Shi L;Zhang Z;Yu AM;Wang W;Wei Z;Akhter E;Maurer K;Costa Reis P;Song L;Petri M;Sullivan KE
对系统性红斑狼疮 (SLE) 患者外周血单核细胞的基因表达研究表明，I 型干扰素特征和炎症细胞因子基因的表达增加。对 Aicardi Goutières 综合征（通常被认为是 SLE 的单基因模型）患者的研究表明，非编码 RNA 的积累可能驱动一些病理基因表达，然而，尚未对 SLE 患者进行 RNA 测序研究。本研究旨在定义编码和非编码 RNA 的表达改变，并检测 SLE 中 RNA 加工的整体改变。使用 RNA-seq 对来自 8 名健康年龄/性别匹配对照和 9 名 SLE 患者（具有低中度疾病活动性且缺乏生物药物使用或免疫抑制治疗）的纯化单核细胞进行了研究。使用定量 RT-PCR 来验证研究结果。通过ELISA测定血清内毒素水平。我们发现 SLE 患者大多数内源性逆转录病毒和小核仁 RNA 的表达减少，但 pri-miRNA 的表达增加。剪接模式和聚腺苷酸化显着改变。此外，SLE 单核细胞表达新的转录物，LPS 处理对照单核细胞也能复制这种效应。我们进一步发现 SLE 患者循环内毒素增加。 SLE 患者的单核细胞表现出整体基因表达失调。 SLE 中的转录组并非简单地通过一组基因的转录激活而改变，而且在性质上有所不同。由 LPS 诱导的新位点的鉴定表明，慢性微生物易位可能导致 SLE 的免疫失调，这是一种新的潜在疾病机制。
Gene expression studies of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) have demonstrated a type I interferon signature and increased expression of inflammatory cytokine genes. Studies of patients with Aicardi Goutières syndrome, commonly cited as a single gene model for SLE, have suggested that accumulation of non-coding RNAs may drive some of the pathologic gene expression, however, no RNA sequencing studies of SLE patients have been performed. This study was designed to define altered expression of coding and non-coding RNAs and to detect globally altered RNA processing in SLE. Purified monocytes from eight healthy age/gender matched controls and nine SLE patients (with low-moderate disease activity and lack of biologic drug use or immune suppressive treatment) were studied using RNA-seq. Quantitative RT-PCR was used to validate findings. Serum levels of endotoxin were measured by ELISA. We found that SLE patients had diminished expression of most endogenous retroviruses and small nucleolar RNAs, but exhibited increased expression of pri-miRNAs. Splicing patterns and polyadenylation were significantly altered. In addition, SLE monocytes expressed novel transcripts, an effect that was replicated by LPS treatment of control monocytes. We further identified increased circulating endotoxin in SLE patients. Monocytes from SLE patients exhibit globally dysregulated gene expression. The transcriptome is not simply altered by the transcriptional activation of a set of genes, but is qualitatively different in SLE. The identification of novel loci, inducible by LPS, suggests that chronic microbial translocation could contribute to the immunologic dysregulation in SLE, a new potential disease mechanism.
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影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
32.4
作者：
Gall A;Treuting P;Elkon KB;Loo YM;Gale M Jr;Barber GN;Stetson DB
通讯作者：
Stetson DB
影响因子：
9.1
作者：
Chauhan, Sudhir Kumar;Singh, Vikas Vikram;Rai, Geeta
通讯作者：
Rai, Geeta
影响因子：
15.3
作者：
IZUI, S;LAMBERT, PH;MIESCHER, PA
通讯作者：
MIESCHER, PA
影响因子：
8.8
作者：
CASEY, WF;HAUSER, GJ;KHAN, WN
通讯作者：
KHAN, WN