期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms20235903
关键词
islet-derived exosomes; mRNA; long noncoding RNA; small noncoding RNA; total RNA sequencing; small RNA sequencing
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-093954, UC4-DK-104166]
- U.S. Department of Veterans Affairs Merit Award [I01BX001733]
- JDRF Strategic Research Award [2-SRA-2018-493-A-B]
- JDRF postdoctoral fellowship [3-PDF-2016-199-A-N]
Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet beta cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1 beta and IFN-gamma. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change >= 1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.
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