Genome Wide Analysis of Gene Expression Changes in Skin from Patients with Type 2 Diabetes
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ABSTRACT: We investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic).
Project description:Clinical skin manifestations are common in diabetes; however, molecular mechanisms underlying such defects are largely unknown. Several findings indicate a role for microRNA (miRNA) in skin homeostasis. We investigated whether miRNA expression is altered in the skin of a Type 1 mouse model of diabetes. For this purpose, miRNA profiling by microarray analysis was performed on RNA extracted from the skin of diabetic mice and non-diabetic controls. >400 different miRNA species were identified, differential expression-analysis revealed miRNA dysregulation in diabetic skin. Interestingly, among the 30 most significantly modulated genes, 27 were downregulated and 3 were upregulated in diabetic mice. Pathway analysis using Tarbase showed an enrichment of signature-miRNA target genes in pathways with roles in skin homeostasis, such as TGF-β and Wnt.
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach—SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography—Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell–cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer’s and Parkinson’s, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.
Project description:Gene expression profiles of biopsy samples of visceral adipose of three female patients of type 2 diabetes and three non-diabetic female patients were generated using Illumina HumanHT-12 v3 Expression BeadChip arrays. The primary indications of surgery were non-infective and non-malignant conditions, namely, cholelethiasis, hernia and trauma.
Project description:Gene expression profiles of biopsy samples of subcutaneous adipose of three female patients of type 2 diabetes and three non-diabetic female patients were generated using Illumina HumanHT-12 v3 Expression BeadChip arrays. The primary indications of surgery were non-infective and non-malignant conditions, namely, cholelethiasis, hernia and trauma.
Project description:Gene expression profiles of biopsy samples of skeletal muscle of three male patients of type 2 diabetes and three non-diabetic male patients were generated using Illumina HumanHT-12 v3 Expression BeadChip arrays. The primary indications of surgery were non-infective and non-malignant conditions, namely, cholelethiasis, hernia and trauma.
Project description:Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. To further identify the roles of LncRNAs in diabetic wound healing, four STZ induced diabetic rat skin tissues and four control rat skin tissues were prepared for a LncRNAs microarray expression profiling by using rat LncRNA Array (4 x 44K, Arraystar).
Project description:We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, cholesterol and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes.
Project description:Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will provide opportunities for more treatment options and better control of disease progression. Effective biomarkers, which are not currently available, may improve clinical outcomes through precise diagnosis and prognosis. We sought to develop a non-invasive diagnostic approach for diabetic retinopathy among type 2 diabetes mellitus based on 5-hydroxymethylcytosines (5hmC), an emerging epigenetic marker, in circulating cell-free DNA (cfDNA)
Project description:We analyzed non-atherosclerotic repair arteries gathered at coronary by-pass operations from 30 patients with type 2 diabetes, as well as from 30 age- and gender-matched non-diabetic individuals. Quantitative proteome analysis was done by iTRAQ-labelling and LC-MS/MS analysis on individual arterial samples. The amounts of the basement membrane (BM) components, alpha-1- and alpha-2- type IV collagen, gamma-1- and beta-2-laminin were significantly increased in patients with diabetes. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users, as compared to non-users. Patients treated with or without metformin had similar levels of HbA1c, cholesterol and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes.