Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals
Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals
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DOI：
10.1007/s00109-005-0721-x
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发表时间：
2005-12-01
影响因子：
4.7
通讯作者：
Inoko, H
中科院分区：
文献类型：
--
作者：
Kulski, JK;Kenworthy, W;Inoko, H
对7名日本患者的受累和未受累银屑病皮肤以及正常皮肤的活检样本进行了基因表达谱分析，以深入了解控制该疾病的通路。研究中使用了包含约12,000个特征明确的人类基因的寡核苷酸阵列的HUG95A Affymetrix DNA芯片。基于学生t检验统计量的排名对Affymetrix数据进行的统计分析揭示了分子应激和免疫基因反应的复杂调控。在受累和未受累银屑病皮肤中诱导的266个基因中，大多数与干扰素介导、免疫、细胞黏附、细胞骨架重构、蛋白质运输和降解、RNA调节和降解、信号转导、细胞凋亡以及非典型表皮细胞增殖和分化有关。皮肤正常蛋白质降解平衡的紊乱反映在各种蛋白酶抑制剂和蛋白酶基因表达的显著增加上，包括参与肽加工和呈递给T细胞的ATP/泛素依赖性非溶酶体蛋白水解途径的诱导成分。一些上调的基因，如TGM1、IVL、FABP5、CSTA和SPRR，是参与非典型表皮细胞组织和分化的众所周知的银屑病标志物。在受累和未受累银屑病皮肤的比较中，转录因子JUNB在受累皮肤上调基因的统计排名中位居前列，这表明它在银屑病中具有重要但尚未明确的作用。我们的基因表达数据和分析表明，银屑病是一种由干扰素和T细胞介导的慢性皮肤免疫疾病，其中表皮细胞结构、生长和分化的失衡源于引发不适当免疫反应的分子抗病毒应激信号。
Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. HUG95A Affymetrix DNA chips that contained oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student t-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signalling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases, including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T cells. Some of the up-regulated genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the up-regulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic interferon- and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.