Up-regulated gene expression in the conjunctival epithelium of patients with Sjogren's syndrome
Up-regulated gene expression in the conjunctival epithelium of patients with Sjogren's syndrome
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DOI：
10.1016/s0014-4835(03)00087-3
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Okubo, K
中科院分区：
文献类型：
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作者：
Kawasaki, S;Kawamoto, S;Okubo, K
目的.通过比较正常人和干燥综合征（SS）患者结膜上皮细胞基因表达谱，阐明SS患者眼表异常的发病机制。研究人群包括56名受试者（26名SS患者和30名正常志愿者）。从他们的结膜上皮细胞提取的RNA进行引入扩增片段长度多态性（iAFLP），竞争性PCR为基础的基因表达测定，以测量基因表达的56个样本对931个基因。资料分析采用二维聚类分析和判别分析。筛选出与疾病相关的基因，并探讨基于基因表达诊断SS的可行性。二维聚类和判别分析清楚地区分SS患者和正常人。在检测的931个基因中，34个在SS中显著上调，12个显著下调（p < 0.05）。上调的基因包括激肽释放酶7（x 15.8）和小脯氨酸丰富的蛋白2A（x 9.6），表皮终末分化的标志物，以及炎症相关基因HLA-DR和IL-6。γ-干扰素诱导的单核因子，即c-fos、纤连蛋白、双调蛋白、防御素β 2和角蛋白16、-6b和-6c也上调。在12个下调基因中，以干扰素γ受体I的下调最为显著（X1/27-3）。角蛋白6和-16、小的富含脯氨酸的蛋白2A和激肽释放酶7在SS患者的结膜上皮中的上调表达提示异常角化模式。上皮增厚可能是由于双调蛋白和/或c-fos刺激的细胞周期进程。γ-干扰素诱导的单核细胞因子、HLA-DR、角蛋白6 b、-6c和-16的上调表明，在SS中，γ-干扰素可能在结膜上皮中改变的基因表达中起重要作用。(C)2003爱思唯尔科技有限公司版权所有。
Purpose. To elucidate the pathogenesis of ocular surface abnormalities in patients with Sjogren's syndrome (SS) by comparing global gene expression patterns in conjunctival epithelial cells from normal individuals and SS patients.Methods. The study population consisted of 56 subjects (26 SS patients and 30 normal volunteers). RNA extracted from their conjunctival epithelial cells was subjected to introduced amplified fragment length polymorphism (iAFLP), a competitive PCR-based gene expression assay, to measure gene expression in the 56 samples against 931 genes. Data were analyzed by two-dimensional clustering analysis and discriminant analysis. Disease-related genes were identified and the feasibility of gene expression-based diagnosis of SS was examined.Results. Two-dimensional clustering- and discriminant analysis clearly distinguished between SS patients and normal subjects. Of 931 genes tested, 34 were significantly up-regulated and 12 were significantly down-regulated in SS (p < 0.05). Up-regulated genes included kallikrein 7 ( x 15.8) and small proline-rich protein 2A ( x 9.6), markers for the terminal differentiation of epidermis, and the inflammation-related genes HLA-DR and IL-6. Monokine-induced-by-gamma-interferon, i.e. c-fos, fibronectin, amphiregulin, defensin beta 2, and keratin 16, -6b and -6c were also up-regulated. Among the 12 down-regulated genes, interferon-gamma receptor I was most notable ( X 1/27-3).Conclusions. The up-regulated expression of keratin 6 and -16, small proline-rich protein 2A, and kallikrein 7 in the conjunctival epithelium of SS patients suggests an anomalous keratinization pattern. Epithelial thickening may be due to amphiregulin and/or c-fos-stimulated cell cycle progression. The up-regulation of monokine-induced-by-gamma-interferon, HLA-DR, keratin 6b, -6c, and -16 suggests that in SS, interferon-gamma may play an important role in the altered gene expression in the conjunctival epithelium. (C) 2003 Elsevier Science Ltd. All rights reserved.