Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection.
Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection.
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DOI：
10.18632/oncotarget.16118
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发表时间：
2017-05-23
期刊：
影响因子：
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通讯作者：
Lee CT
中科院分区：
文献类型：
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作者：
Wu C;Chen X;Shu J;Lee CT
皮肤病是2型糖尿病（T2 DM）最常见的并发症之一。尽管已知T2 DM患者感染和其他T2 DM相关皮肤疾病的风险增加，但其分子机制在很大程度上尚不清楚。本研究旨在确定与人类皮肤中T2 DM相关的失调基因和基因网络。我们比较了来自基因型组织表达（GTEx）数据库的74例T2 DM病例和148例性别、年龄和种族匹配的非糖尿病对照的56,318个转录基因的表达谱。RNA测序数据表明，糖尿病皮肤的特征在于与免疫应答（CCL 20、CXCL 9、CXCL 10、CXCL 11、CXCL 13和CCL 18）、JAK/STAT信号通路（JAK 3、STAT 1和STAT 2）、肿瘤坏死因子超家族（TNFSF 10和TNFSF 15）和感染性疾病通路（OAS 1、OAS 2、OAS 3和IFIH 1）相关的基因表达增加。细胞粘附分子通路（NCAM 1和L1 CAM）和胶原蛋白家族（PCOLCE 2和COL 9A 3）中的基因下调，提示T2 DM皮肤的结构改变。据我们所知，这项先驱分析研究首次报告了T2 DM患者非病变皮肤中全面无偏的基因表达变化和失调途径。这种来自全基因组表达谱的全面理解可以推进我们在确定预防和治疗T2 DM相关皮肤疾病的分子靶点方面的知识。
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data indicates that diabetic skin is characterized by increased expression of genes that are related to immune responses (CCL20, CXCL9, CXCL10, CXCL11, CXCL13, and CCL18), JAK/STAT signaling pathway (JAK3, STAT1, and STAT2), tumor necrosis factor superfamily (TNFSF10 and TNFSF15), and infectious disease pathways (OAS1, OAS2, OAS3, and IFIH1). Genes in cell adhesion molecules pathway (NCAM1 and L1CAM) and collagen family (PCOLCE2 and COL9A3) are downregulated, suggesting structural changes in the skin of T2DM. For the first time, to the best of our knowledge, this pioneer analytic study reports comprehensive unbiased gene expression changes and dysregulated pathways in the non-diseased skin of T2DM patients. This comprehensive understanding derived from whole-genome expression profiles could advance our knowledge in determining molecular targets for the prevention and treatment of T2DM-associated skin disorders.