Research Paper Volume 10, Issue 12 pp 3986—3999

Injury factors alter miRNAs profiles of exosomes derived from islets and circulation

Qi Fu 1, *, , Hemin Jiang 1, *, , Zibin Wang 2, *, , Xingyun Wang 3, , Heng Chen 1, , Ziyang Shen 1, , Lei Xiao 1, , Xirong Guo 3, , Tao Yang 1, ,

  • 1 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
  • 2 Analysis Center, Nanjing Medical University, Nanjing, Jiangsu 211166, China
  • 3 Nanjing Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, China
* Equal contribution

received: June 29, 2018 ; accepted: November 26, 2018 ; published: December 14, 2018 ;

https://doi.org/10.18632/aging.101689
How to Cite

Copyright: Fu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Islets damage is a major abnormality underling diabetes. Recent studies suggested the value of exosomes in diagnosis. This study aimed to investigate the impact of injury factors on the miRNA profiles of islet exosomes and determine whether circulating exosomal miRNAs is suitable as biomarkers of islets damage. Islets were isolated from ICR mice and induced injury in vitro by mixed cytokines (Tumor Necrosis Factor-α, Interleukin -1β and Interferon-γ) or streptozotocin (STZ), and exosomes were derived from the cultural supernatant. Using miRNA microarray analysis, we found 22 and 11 differentially expressed miRNAs in islet exosomes of STZ and cytokines treatment, respectively, including 6 miRNAs as the intersection of two injured conditions. Thereinto, mmu-miR-375-3p and mmu-miR-129-5p could be validated by qRT-PCR. Then, Serum exosomes were isolated from STZ injected mice and subjects with various glucose metabolism states and diabetic duration. qRT-PCR demonstrated exosomal mmu-miR-375-3p dramatically increased in serum of STZ treated mouse prior to the disturbance of blood glucose and insulin. In human serum exosomes, hsa-miR-375-3p was elevated in new-onset diabetes patients. Overall, our results suggest that injury factors changed miRNA profiles of exosomes derived from islets and exosomal miR-375-3p showed promising potential as a biomarker of islets damage.

Abbreviations

AO/PI: Acridine orange/Propidium iodide; AUC: Area under curve; Bax: Bcl-2 associated X protein; Chop: C/EBP homologous protein; ERS: Endoplasmic reticulum stress; EVs: Extracellular vesicles; FBS: Fetal bovine serum; HBSS: Hanks’ balanced salt solution; IFNγ: Interferon γ; IGT: Impaired glucose tolerance; IL-1β: Interleukin-1 β; MMTT: Mixed meal tolerance test; ncRNA: Noncoding RNA; NGT: normal glucose tolerance; NTA: Nanoparticle tracking analysis; PBS: Phosphate saline buffer; qRT-PCR: Real-time quantitative PCR; STZ: Streptozotocin; T1DM: Type 1 diabetes; T2DM: Type 2 diabetes; TEM: Transmission Electron Microscopy; TNFα: tumor necrosis factor α.