Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital

Plasma Exosome-Enriched Extracellular Vesicles From Lactating Mothers With Type 1 Diabetes Contain Aberrant Levels of miRNAs During the Postpartum Period

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Migration, gestational diabetes and adverse pregnancy outcomes: a nationwide study of singleton deliveries in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Academic performance in adolescents born to mothers with gestational diabetes - a national Danish cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Gestational diabetes mellitus and stigma: A scoping review

    Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  • Caroline Frørup
  • Aashiq H Mirza
  • Reza Yarani
  • Lotte B Nielsen
  • Elisabeth R Mathiesen
  • Peter Damm
  • Jens Svare
  • Christian Engelbrekt
  • Joachim Størling
  • Jesper Johannesen
  • Henrik B Mortensen
  • Flemming Pociot
  • Simranjeet Kaur
Vis graf over relationer

Type 1 diabetes is an immune-driven disease, where the insulin-producing beta cells from the pancreatic islets of Langerhans becomes target of immune-mediated destruction. Several studies have highlighted the implication of circulating and exosomal microRNAs (miRNAs) in type 1 diabetes, underlining its biomarker value and novel therapeutic potential. Recently, we discovered that exosome-enriched extracellular vesicles carry altered levels of both known and novel miRNAs in breast milk from lactating mothers with type 1 diabetes. In this study, we aimed to characterize exosomal miRNAs in the circulation of lactating mothers with and without type 1 diabetes, hypothesizing that differences in type 1 diabetes risk in offspring from these groups are reflected in the circulating miRNA profile. We performed small RNA sequencing on exosome-enriched extracellular vesicles extracted from plasma of 52 lactating mothers around 5 weeks postpartum (26 with type 1 diabetes and 26 age-matched controls), and found a total of 2,289 miRNAs in vesicles from type 1 diabetes and control libraries. Of these, 176 were differentially expressed in plasma from mothers with type 1 diabetes (167 upregulated; 9 downregulated, using a cut-off of abs(log2FC) >1 and FDR adjusted p-value <0.05). Extracellular vesicles were verified by nanoparticle tracking analysis, transmission electron microscopy and immunoblotting. Five candidate miRNAs were selected based on their involvement in diabetes and immune modulation/beta-cell functions: hsa-miR-127-3p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p and hsa-miR-30d-5p. Real-time qPCR validation confirmed that hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p, and hsa-miR-30d-5p were significantly upregulated in lactating mothers with type 1 diabetes as compared to lactating healthy mothers. To determine possible target genes and affected pathways of the 5 miRNA candidates, computational network-based analyses were carried out with TargetScan, mirTarBase, QIAGEN Ingenuity Pathway Analysis and PantherDB database. The candidates showed significant association with inflammatory response and cytokine and chemokine mediated signaling pathways. With this study, we detect aberrant levels of miRNAs within plasma extracellular vesicles from lactating mothers with type 1 diabetes during the postpartum period, including miRNAs with associations to disease pathogenesis and inflammatory responses.

TidsskriftFrontiers in Immunology
Sider (fra-til)744509
StatusUdgivet - 8 okt. 2021

Bibliografisk note

Copyright © 2021 Frørup, Mirza, Yarani, Nielsen, Mathiesen, Damm, Svare, Engelbrekt, Størling, Johannesen, Mortensen, Pociot and Kaur.

ID: 69077075