Genetic Signatures From RNA Sequencing of Pediatric Localized Scleroderma Skin.
Genetic Signatures From RNA Sequencing of Pediatric Localized Scleroderma Skin.
复制标题
DOI：
10.3389/fped.2021.669116
复制
发表时间：
2021
影响因子：
2.6
通讯作者：
Torok KS
中科院分区：
文献类型：
--
作者：
Mirizio E;Liu C;Yan Q;Waltermire J;Mandel R;Schollaert KL;Konnikova L;Wang X;Chen W;Torok KS
本研究的目的是探索儿童局限性硬皮病(LS)的皮肤转录谱，以更好地了解促进疾病的免疫和纤维化途径的改变。LS是一种进行性皮肤和底层组织疾病，会导致严重的功能残疾和毁容，尤其是在发育中的儿童。RNA测序(RNAseq)技术允许通过对LS疾病进展阶段(更活跃/炎症与更不活跃/纤维化)的转录组分析来改进对相关细胞表达的理解，并允许使用从现有的石蜡包埋皮肤组织中提取的RNA，这在儿科中非常重要。在健康受试者和LS受试者新鲜皮肤(RNAlater)和石蜡组织之间的基因表达的比较中观察到了强烈的相关性，支持使用石蜡组织。LS基因特征与健康对照组相比，显示了由干扰素γ-、干扰素α-和肿瘤坏死因子α相关基因组成的炎症反应基因特征的明显表达。GSEA©富集分析显示，在炎性病变较多的LS患者中，包括干扰素诱导的趋化因子CXCL9、CXCL10、CXCL11和干扰素γ本身在内的IRGS的表达水平更高。通过比较基因表达谱，证明石蜡皮肤用于测序是一种有效的替代新鲜皮肤的方法。活动期LS患者皮损组织中干扰素γ信号的流行表明，这些基因反映了临床活动参数，可能是早期炎症性疾病的启动子。
The purpose of this study was to explore the skin transcriptional profile in pediatric localized scleroderma (LS) to provide a better understanding of the altered immune and fibrotic pathways promoting disease. LS is a progressive disease of the skin and underlying tissue that causes significant functional disability and disfigurement, especially in developing children. RNA sequencing (RNAseq) technology allows for improved understanding of relevant cellular expression through transcriptome analysis of phases during LS disease progression (more active/inflammatory vs. inactive/fibrotic) and also permits the use of RNA extracted from existing paraffin-embedded skin tissue, which is important in pediatrics. A strong correlation was observed between the comparison of genes expressed between fresh (RNAlater) and paraffinized skin in healthy and LS subjects, supporting the use of paraffinized tissue. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ-, IFNα-, and TNFα-associated genes. GSEA© enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNγ itself, was more highly expressed in LS patients with more inflammatory lesions. The use of paraffinized skin for sequencing was proven to be an effective substitute for fresh skin by comparing gene expression profiles. The prevalence of the IFNγ signature in the lesion biopsies of active LS patients indicates that these genes reflect clinical activity parameters and may be the promoters of early, inflammatory disease.
登录
查看更多内容
影响因子：
5.8
作者：
Angel, P;Szabowski, A
通讯作者：
Szabowski, A
影响因子：
7
作者：
Cieslik M;Chugh R;Wu YM;Wu M;Brennan C;Lonigro R;Su F;Wang R;Siddiqui J;Mehra R;Cao X;Lucas D;Chinnaiyan AM;Robinson D
通讯作者：
Robinson D
影响因子：
3.8
作者：
Jovanović B;Sheng Q;Seitz RS;Lawrence KD;Morris SW;Thomas LR;Hout DR;Schweitzer BL;Guo Y;Pietenpol JA;Lehmann BD
通讯作者：
Lehmann BD
局部的硬皮病皮肤严重程度指数和医师全球疾病活动评估：旨在发展局部硬皮病预后指标的工作。
DOI：
10.3899/jrheum.081284
发表时间：
2009-12
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Arkachaisri T;Vilaiyuk S;Li S;O'Neil KM;Pope E;Higgins GC;Punaro M;Rabinovich EC;Rosenkranz M;Kietz DA;Rosen P;Spalding SJ;Hennon TR;Torok KS;Cassidy E;Medsger TA Jr;Localized Scleroderma Clinical and Ultrasound Study Group
通讯作者：
Localized Scleroderma Clinical and Ultrasound Study Group
影响因子：
--
作者：
Bulatovic, Maja;Heijstek, Marloes W.;Wulffraatl, Nico M.
通讯作者：
Wulffraatl, Nico M.