Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Takematsu, Eri; Spencer, Adrianne; Auster, Jeff; Chen, Po-Chih; Graham, Annette; Martin, Patricia; Baker, Aaron

doi:10.1371/journal.pone.0225267

Cited by 24 publications

(23 citation statements)

References 109 publications

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“…An animal study showed that LRP1 expression was increased in cardiomyocytes isolated from acutely diabetic rats [22]. Other studies reported the upregulation of LRP1 in epicardial fat and skin from diabetic patients compared with control individuals, which was consistent with our findings [23,24]. In contrast, another study showed a significant reduction in LRP1 expression in subjects with diabetic peripheral neuropathy compared with the noncomplication group [25].…”

Section: Discussionsupporting

confidence: 90%

Identification of Susceptibility Modules and Genes for Cardiovascular Disease in Diabetic Patients Using WGCNA Analysis

Liang

Sun

Zhao

et al. 2020

Journal of Diabetes Research

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Objective. To identify susceptibility modules and genes for cardiovascular disease in diabetic patients using weighted gene coexpression network analysis (WGCNA). Methods. The raw data of GSE13760 were downloaded from the Gene Expression Omnibus (GEO) website. Genes with a false discovery rate<0.05 and a log2 fold change≥0.5 were included in the analysis. WGCNA was used to build a gene coexpression network, screen important modules, and filter the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the genes in modules with clinical interest. Genes with a significance over 0.2 and a module membership over 0.8 were used as hub genes. Subsequently, we screened these hub genes in the published genome-wide SNP data of cardiovascular disease. The overlapped genes were defined as key genes. Results. Fourteen gene coexpression modules were constructed via WGCNA analysis. Module greenyellow was mostly significantly correlated with diabetes. The GO analysis showed that genes in the module greenyellow were mainly enriched in extracellular matrix organization, extracellular exosome, and calcium ion binding. The KEGG analysis showed that the genes in the module greenyellow were mainly enriched in antigen processing and presentation, phagosome. Fifteen genes were identified as hub genes. Finally, HLA-DRB1, LRP1, and MMP2 were identified as key genes. Conclusion. This was the first study that used the WGCNA method to construct a coexpression network to explore diabetes-associated susceptibility modules and genes for cardiovascular disease. Our study identified a module and several key genes that acted as essential components in the etiology of diabetes-associated cardiovascular disease, which may enhance our fundamental knowledge of the molecular mechanisms underlying this disease.

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Section: Discussionsupporting

confidence: 90%

Identification of Susceptibility Modules and Genes for Cardiovascular Disease in Diabetic Patients Using WGCNA Analysis

Liang

Sun

Zhao

et al. 2020

Journal of Diabetes Research

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“…In general terms, the differential global gene expression in the skin of the diabetic humanized mice (D0vsC0) closely reproduced the cutaneous transcriptome profiling in diabetic patients [ 37 , 38 ]. Specifically, those studies showed altered GO_BPs and KEGG pathways related to focal adhesions, cell adhesions mediated by integrins, and ECM-related processes, as in our diabetic skin-humanized mouse model ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 90%

Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response

León

García‐García

Llames

et al. 2020

Genes

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Defective healing leading to cutaneous ulcer formation is one of the most feared complications of diabetes due to its consequences on patients’ quality of life and on the healthcare system. A more in-depth analysis of the underlying molecular pathophysiology is required to develop effective healing-promoting therapies for those patients. Major architectural and functional differences with human epidermis limit extrapolation of results coming from rodents and other small mammal-healing models. Therefore, the search for reliable humanized models has become mandatory. Previously, we developed a diabetes-induced delayed humanized wound healing model that faithfully recapitulated the major histological features of such skin repair-deficient condition. Herein, we present the results of a transcriptomic and functional enrichment analysis followed by a mechanistic analysis performed in such humanized wound healing model. The deregulation of genes implicated in functions such as angiogenesis, apoptosis, and inflammatory signaling processes were evidenced, confirming published data in diabetic patients that in fact might also underlie some of the histological features previously reported in the delayed skin-humanized healing model. Altogether, these molecular findings support the utility of such preclinical model as a valuable tool to gain insight into the molecular basis of the delayed diabetic healing with potential impact in the translational medicine field.

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“…Takematsu et al examined the changes in gene expression in the skin between 13 patients with type 2 diabetes and 14 non-diabetic patients. 33 They found that the most upregulated genes included three lncRNAs: LINC01118, RP11545I5.3, and an unknown lncRNA. In contrast, the most downregulated genes included three lncRNAs: LINC01060, HPRT1P2, and CCNYL3.…”

Section: Lncrna Expression Profiling In Diabetic Foot Ulcersmentioning

confidence: 99%

Emerging Roles of Long Non-Coding RNAs in Diabetic Foot Ulcers

Yan

Chen

Yang

et al. 2021

DMSO

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Diabetes mellitus is one of the most widespread metabolic diseases in the world, and diabetic foot ulcer (DFU), as one of its chronic complications, not only causes a large amount of physiological and psychological pain to patients but also places a tremendous burden on the entire economy and society. Despite significant advances in knowledge on the mechanism and in the treatment of DFU, clinical practice is still not satisfactory, and our understanding of its cellular and molecular pathogenesis is far from complete. Fortunately, progress in studying the roles of long non-coding RNAs (lncRNAs), which play important regulatory roles in the expression of genes at multiple levels, suggests that we can apply them in the early diagnosis and potential targeted intervention of DFU. In this review, we briefly summarize the current knowledge regarding the functional roles and potential mechanisms of reported lncRNAs in regulating DFU.

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Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Abstract: Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials.

Cited by 24 publications

References 109 publications

Identification of Susceptibility Modules and Genes for Cardiovascular Disease in Diabetic Patients Using WGCNA Analysis

Identification of Susceptibility Modules and Genes for Cardiovascular Disease in Diabetic Patients Using WGCNA Analysis

Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response

Emerging Roles of Long Non-Coding RNAs in Diabetic Foot Ulcers

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