Profiling of RNAs from human islet-derived exosomes in a model of type 1 diabetes

Preethi Krishnan, Farooq Syed, Nicole Jiyun Kang, Raghavendra G. Mirmira, Carmella Evans-Molina

Research output: Contribution to journalArticle

Abstract

Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β 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-1β and IFN-γ. 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.

Original languageEnglish (US)
Article number5903
JournalInternational journal of molecular sciences
Volume20
Issue number23
DOIs
StatePublished - Dec 1 2019

Fingerprint

Exosomes
biomarkers
Medical problems
RNA
Type 1 Diabetes Mellitus
insulin
coding
Untranslated RNA
secretions
Biomarkers
sequencing
necrosis
apoptosis
Cytokines
Islets of Langerhans
destruction
catalogs
Exosome Multienzyme Ribonuclease Complex
calcium
Long Noncoding RNA

Keywords

  • Islet-derived exosomes
  • Long noncoding RNA
  • MRNA
  • Small noncoding RNA
  • Small RNA sequencing
  • Total RNA sequencing

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Profiling of RNAs from human islet-derived exosomes in a model of type 1 diabetes. / Krishnan, Preethi; Syed, Farooq; Kang, Nicole Jiyun; Mirmira, Raghavendra G.; Evans-Molina, Carmella.

In: International journal of molecular sciences, Vol. 20, No. 23, 5903, 01.12.2019.

Research output: Contribution to journalArticle

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