What does global gene expression profiling tell us about the pathogenesis of systemic sclerosis?

What does global gene expression profiling tell us about the pathogenesis of systemic sclerosis?
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DOI:
10.1097/01.bor.0000434672.77891.41
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发表时间:
2013-11
影响因子:
5.1
通讯作者:
Mayes MD
Mayes MD
中科院分区:
医学2区
文献类型:
--
作者:
Assassi S;Mayes MD

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这项研究的目的是回顾最近利用全球基因表达数据来阐明系统性硬化症(SSC)及其各种临床表现的分子基础的假说驱动的研究。纵向皮肤基因表达研究表明,先前确定的分子亚群随着时间的推移是稳定的,并可能识别SSC患者的固有亚群。皮肤转录跟踪研究表明,Wnt/β-连环蛋白通路在促进成纤维细胞和前脂肪细胞的纤维化过程中发挥着重要作用。此外,硬皮病型移植物抗宿主病(SclGVHD)小鼠的转录谱类似于具有IL13/IL4诱导皮肤特征的SSC患者亚群的皮肤转录谱,其中促纤维化趋化因子CCL2起关键作用。SSC患者的皮肤活检与皮肤狼疮和皮肌炎患者的皮肤病变的比较为这些自身免疫性疾病中的干扰素信号提供了有价值的信息。此外,血浆干扰素诱导的趋化因子与自发性硬化症患者的干扰素基因表达分数相关,使研究人员能够通过血清或血浆采集在大型自发性硬化性硬化症队列中检验这一分子特征。皮肤和外周血中的全球基因表达谱有助于更好地了解SSC的发病机制,并寻找新的生物标志物和治疗靶点。
The purpose of this study is to review recent hypothesis-driven studies that utilize global gene expression data for elucidating the molecular basis of systemic sclerosis (SSc) and its various clinical manifestations. The longitudinal skin gene expression studies indicate that the previously identified molecular subsets are stable over time and might identify inherent subgroups of SSc patients. Skin transcript follow-up studies indicate that the Wnt/β-catenin pathway plays an important role in promotion of fibrogenesis in fibroblasts and preadipocytes. Furthermore, the transcript profile of sclerodermatous graft-versus-host disease (sclGVHD) mice resembles the skin transcriptomes of a subgroup of SSc patients with IL13/IL4-inducible skin signature wherein the profibrotic chemokine CCL2 plays a key role. The comparison of skin biopsies from SSc patients to skin lesions of patients with cutaneous lupus and dermatomyositis has provided valuable information about the interferon (IFN) signature in these autoimmune diseases. Furthermore, plasma IFN-inducible chemokines correlate with the IFN gene expression score in SSc patients, enabling researchers to examine this molecular signature in large SSc cohorts with serum or plasma collection. Global gene expression profiling in skin and peripheral blood can contribute to a better understanding of SSc pathogenesis and identify novel biomarkers and therapeutic targets.
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