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Network analysis reveals dysregulated functional patterns in type II diabetic skin
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Network analysis reveals dysregulated functional patterns in type II diabetic skin
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Journal Article
Network analysis reveals dysregulated functional patterns in type II diabetic skin
2022
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
