Identification of hub genes related to silicone-induced immune response in rats.

Identification of hub genes related to silicone-induced immune response in rats.
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与硅诱导的大鼠免疫反应相关的中枢基因的鉴定

DOI:
10.18632/oncotarget.21546
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发表时间:
2017-11-21
期刊:
影响因子:
--
通讯作者:
Li Q
Li Q
中科院分区:
其他
文献类型:
--
作者:
Huang X;Zhou Y;Liu W;Li H;Liang X;Jin R;Du H;He J;Chai B;Duan R;Li Q

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硅胶植入物广泛应用于整形外科领域,并用于大量人群。然而,它们的安全性,特别是硅胶诱导的免疫反应,几十年来一直是整形外科医生的主要关注点。有人假设硅胶和免疫力之间存在因果关系,但这是有争议的。本研究的目的是在大鼠模型中确定与硅胶植入物诱导的免疫反应相关的中枢基因和关键途径。除了聚类和富集分析,我们还使用加权基因共表达网络分析(WGCNA)来系统地研究基因表达谱。共确定了5个基因(Fes、Aif1、Gata3、Tlr6、Tlr2)为最可能与硅胶诱导的免疫应答相关的中枢基因,其中4个(Aif1、Gata3、Tlr6、Tlr2)作为靶基因或疾病标志物与自身免疫相关。Toll样受体信号通路(p < 0.01,富集倍数:7.01)和系统性红斑狼疮信号通路(p < 0.05,富集倍数:5.01)被认为与自身免疫性强相关,在硅胶植入皮肤样本中显著富集。结果表明,硅胶植入可能引发局部免疫反应,因为硅胶植入后检测到各种免疫反应基因。这五个基因有望成为硅橡胶相关并发症和相关自身免疫性疾病的新的治疗靶点。
Silicone implants are used widely in the field of plastic surgery and are used in a large population. However, their safety profile, especially the silicone-induced immune response, has been a major concern for plastic surgeons for decades. It has been hypothesized that there is a cause and effect relation between silicone and immunity, but this is controversial. The objective of the present study was to determine the hub genes and key pathways related to silicone implant–induced immune responses in a rat model. In addition to cluster and enrichment analyses, we used weighted gene co-expression network analysis (WGCNA) to examine the gene expression profiles in a systematic context. A total five genes (Fes, Aif1, Gata3, Tlr6, Tlr2) were identified as hub genes that are most likely related to the silicone-induced immune response, four of which (Aif1, Gata3, Tlr6, Tlr2) have been associated with autoimmunity as target genes or disease markers. The Toll-like receptor signaling pathway (p < 0.01, fold enrichment: 7.01) and systemic lupus erythematosus signaling pathway (p < 0.05, fold enrichment: 5.01), which are considered strongly associated with autoimmunity, were significantly enriched in the silicone-implanted skin samples. The results indicate that silicone implants might trigger the localized immune response, as various immune reaction genes were detected after silicone implantation. The identified five hub genes will hopefully serve as novel therapeutic targets for silicone-related complications and the associated autoimmune diseases.
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