Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways.
Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways.
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DOI：
10.1371/journal.pone.0120917
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Falciani F
中科院分区：
文献类型：
--
作者：
Filer A;Antczak P;Parsonage GN;Legault HM;O'Toole M;Pearson MJ;Thomas AM;Scheel-Toellner D;Raza K;Buckley CD;Falciani F
持续性炎症性关节炎中的滑膜成纤维细胞被认为与癌症生长和伤口愈合有相似之处，两者都涉及一个典型的血清反应程序。我们检验了血清反应程序可用于分类病变组织的假设，并研究了来自多个解剖部位和两种疾病的成纤维细胞的血清反应程序。为了验证我们的假设，我们利用生物信息学方法探索了一个公开可用的微阵列数据集，包括类风湿关节炎（RA）、骨关节炎（OA）和正常滑膜组织，然后在一个新的微阵列数据集中扩展了这些发现，该数据集代表了从接受关节置换术的RA和OA患者培养的匹配的滑膜、骨髓和皮肤成纤维细胞。经典的成纤维细胞血清反应程序可将RA、OA和正常滑膜组织分离。对低血清和高血清处理的成纤维细胞微阵列数据的分析揭示了控制的层次结构，解剖部位是最强大的分类器，其次是对血清的反应，然后是疾病。与皮肤和骨髓成纤维细胞相比，滑膜成纤维细胞暴露于血清中导致RA和OA表达谱趋同。通路分析揭示了OA滑膜成纤维细胞的三个相互关联的基因网络：通过胰岛素样生长因子进行细胞重塑，通过_3整合素进行细胞分化和血管生成，通过CD44调控细胞凋亡。我们已经证明成纤维细胞的血清反应特征在组织水平上定义疾病，并且OA特异性的，血清依赖的抑制参与细胞粘附，细胞外基质重塑和凋亡的基因是培养OA和RA滑膜成纤维细胞之间的关键鉴别因子。
Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts.
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影响因子：
--
作者：
Ohshima, S;Kuchen, S;Neidhart, M
通讯作者：
Neidhart, M
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
3.7
作者：
Nguyen, TuDung T.;Ma, Lisa N.;Arber, Daniel A.
通讯作者：
Arber, Daniel A.
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO
影响因子：
--
作者：
Izquierdo, Elena;Canete, Juan D.;Pablos, Jose L.
通讯作者：
Pablos, Jose L.