Oncotarget

Research Papers:

Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection

Chun Wu, Xiaopan Chen, Jing Shu and Chun-Ting Lee _

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Oncotarget. 2017; 8:34601-34609. https://doi.org/10.18632/oncotarget.16118

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Abstract

Chun Wu1, Xiaopan Chen2, Jing Shu2 and Chun-Ting Lee3

1Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL, USA

2Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, P.R. China

3Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA

Correspondence to:

Chun-Ting Lee, email: Chun-Ting.Lee@fda.hhs.gov

Chun Wu, email: c.wu6@med.miami.edu

Keywords: transcriptome, type 2 diabetes, human skin, immune, infection

Received: December 08, 2016    Accepted: February 20, 2017    Published: March 11, 2017

ABSTRACT

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.


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