Network analysis reveals dysregulated functional patterns in type II diabetic skin
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Department of Biosystems Engineering, BIO5 Institute, University of ArizonaDepartment of Management Information Systems, BIO5 Institute, University of Arizona
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2022
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Nature ResearchCitation
Liu, C., Ram, S., & Hurwitz, B. L. (2022). Network analysis reveals dysregulated functional patterns in type II diabetic skin. Scientific Reports.Journal
Scientific reportsRights
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Skin disorders are one of the most common complications of type II diabetes (T2DM). Long-term effects of high blood glucose leave individuals with T2DM more susceptible to cutaneous diseases, but its underlying molecular mechanisms are unclear. Network-based methods consider the complex interactions between genes which can complement the analysis of single genes in previous research. Here, we use network analysis and topological properties to systematically investigate dysregulated gene co-expression patterns in type II diabetic skin with skin samples from the Genotype-Tissue Expression database. Our final network consisted of 8812 genes from 73 subjects with T2DM and 147 non-T2DM subjects matched for age, sex, and race. Two gene modules significantly related to T2DM were functionally enriched in the pathway lipid metabolism, activated by PPARA and SREBF (SREBP). Transcription factors KLF10, KLF4, SP1, and microRNA-21 were predicted to be important regulators of gene expression in these modules. Intramodular analysis and betweenness centrality identified NCOA6 as the hub gene while KHSRP and SIN3B are key coordinators that influence molecular activities differently between T2DM and non-T2DM populations. We built a TF-miRNA-mRNA regulatory network to reveal the novel mechanism (miR-21-PPARA-NCOA6) of dysregulated keratinocyte proliferation, differentiation, and migration in diabetic skin, which may provide new insights into the susceptibility of skin disorders in T2DM patients. Hub genes and key coordinators may serve as therapeutic targets to improve diabetic skincare. © 2022. The Author(s).Note
Open access journalISSN
2045-2322PubMed ID
35477946Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1038/s41598-022-10652-8
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Except where otherwise noted, this item's license is described as © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.
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