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Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.

ABSTRACT: Type 1 diabetes mellitus (T1DM) results from an autoimmune attack against the insulin-producing ß cells which leads to chronic hyperglycemia. Exosomes are lipid vesicles derived from cellular multivesicular bodies that are enriched in specific miRNAs, potentially providing a disease-specific diagnostic signature. To assess the value of exosome miRNAs as biomarkers for T1DM, miRNA expression in plasma-derived exosomes was measured. Nanoparticle tracking analysis and transmission electron microscopy confirmed the presence of plasma-derived exosomes (EXOs) isolated by differential centrifugation. Total RNA extracted from plasma-derived EXOs of 12 T1DM and 12 control subjects was hybridized onto Nanostring human v2 miRNA microarray array and expression data were analyzed on nSolver analysis software. We found 7 different miRNAs (1 up-regulated and 6 down-regulated), that were differentially expressed in T1DM. The selected candidate miRNAs were validated by qRT-PCR analysis of cohorts of 24 T1DM and 24 control subjects. Most of the deregulated miRNAs are involved in progression of T1DM. These findings highlight the potential of EXOs miRNA profiling in the diagnosis as well as new insights into the molecular mechanisms involved in T1DM.

SUBMITTER: Garcia-Contreras M

PROVIDER: S-EPMC5519761 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.

Garcia-Contreras Marta M Shah Sanket H SH Tamayo Alejandro A Robbins Paul D PD Golberg Ronald B RB Mendez Armando J AJ Ricordi Camillo C

Scientific reports 20170720 1

Type 1 diabetes mellitus (T1DM) results from an autoimmune attack against the insulin-producing ß cells which leads to chronic hyperglycemia. Exosomes are lipid vesicles derived from cellular multivesicular bodies that are enriched in specific miRNAs, potentially providing a disease-specific diagnostic signature. To assess the value of exosome miRNAs as biomarkers for T1DM, miRNA expression in plasma-derived exosomes was measured. Nanoparticle tracking analysis and transmission electron microsco ...[more]

PMID: 28729721

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Project description:ImportanceDisease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied.ObjectiveTo investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients.DesignThis study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score ≥3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman's rank correlation coefficients were calculated between metabolites and cytokines.SettingPatients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center.ParticipantsThe study included 20 atopic dermatitis patients and 24 healthy control patients.Main outcomes and measuresFold changes of metabolites in AD vs healthy control plasma.ResultsIn patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values<0.0001) compared to healthy controls. Enriched metabolites were involved in branched-chain amino acid (valine, leucine, and isoleucine) degradation, catecholamine biosynthesis, thyroid hormone synthesis, threonine metabolism, and branched and long-chain fatty acid metabolism. Dysregulated metabolites in AD were positively correlated cytokines TARC and MCP-4 and negatively correlated with IL-1a and CCL20.Conclusions and relevanceOur study characterized novel dysregulated circulating plasma metabolites and metabolic pathways that may be involved in the pathogenesis of AD. These metabolic pathways serve as potential future biomarkers and therapeutic targets in the treatment of AD.

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Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.

Publications

Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.

Similar Datasets

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