4.6 Article

Role and mechanisms of exosomal miRNAs in IBD pathophysiology

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00295.2020

Keywords

exosomes; IBD; miRNA; RNA-binding protein; 3 '-end modification; sorting

Funding

  1. National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK60729, DK47373, DK110003, CURE: DDRC P30 DK 41301]
  2. Crohn's and Colitis Foundation of America, Inc.
  3. Blinder Research Foundation for Crohn's Disease
  4. Eli and Edythe Broad Chair
  5. Broad Foundation

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Exosomes represent secretory membranous vesicles used for the information exchange between cells and organ-to-organ communication. Exosome crosstalk mechanisms are involved in the regulation of several inflammatory bowel disease (IBD)-associated pathophysiological intestinal processes such as barrier function, immune responses, and intestinal flora. Functional biomolecules, mainly noncoding RNAs (ncRNAs), are believed to be transmitted between the mammalian cells via exosomes that likely play important roles in cell-to-cell communication, both locally and systemically. MicroRNAs (miRNAs) encapsulated in exosomes have generated substantial interest because of their critical roles in multiple pathophysiological processes. In addition, exosomal miRNAs are implicated in the gut health. MiRNAs are selectively and actively loaded into the exosomes and then transferred to the target recipient cell where they manipulate cell function through posttranscriptional silencing of target genes. Intriguingly, miRNA profile of exosomes differs from their cellular counterparts suggesting an active sorting and packaging mechanism of exosomal miRNAs. Even more exciting is the involvement of posttranscriptional modifications in the specific loading of miRNAs into exosomes, but the underlying mechanisms of how these modifications direct ncRNA sorting have not been established. This review gives a brief overview of the status of exosomes and exosomal miRNAs in IBD and also discusses potential mechanisms of exosomal miRNA sorting and delivering.

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