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Plasma Exosome-Enriched Extracellular Vesicles From Lactating Mothers With Type 1 Diabetes Contain Aberrant Levels of miRNAs During the Postpartum Period.
Frørup, Caroline; Mirza, Aashiq H; Yarani, Reza; Nielsen, Lotte B; Mathiesen, Elisabeth R; Damm, Peter; Svare, Jens; Engelbrekt, Christian; Størling, Joachim; Johannesen, Jesper; Mortensen, Henrik B; Pociot, Flemming; Kaur, Simranjeet.
Afiliación
  • Frørup C; Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Mirza AH; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Yarani R; Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Nielsen LB; Department of Pharmacology, Weill Cornell Medical, New York, NY, United States.
  • Mathiesen ER; Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Damm P; Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark.
  • Svare J; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Engelbrekt C; Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
  • Størling J; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Johannesen J; Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark.
  • Mortensen HB; Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Pociot F; Department of Obstetrics, Herlev and Gentofte Hospital, Herlev, Denmark.
  • Kaur S; Department of Chemistry, Technical University of Denmark, Lyngby, Denmark.
Front Immunol ; 12: 744509, 2021.
Article en En | MEDLINE | ID: mdl-34691048
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lactancia Materna / Diabetes Mellitus Tipo 1 / Exosomas / MicroARN Circulante Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lactancia Materna / Diabetes Mellitus Tipo 1 / Exosomas / MicroARN Circulante Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza