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Function and Metabolism of MRNA and MicroRNA Cargos in Bovine Milk Exosomes in Non-Bovine Mammals
Exosomes are natural nanoparticles that participate in intercellular communication through transferring their regulatory molecules including mRNA and non-coding RNA, from donor cells to recipient cells. Our laboratory demonstrated that exosomes and their microRNA cargos are not exclusively obtained from endogenous synthesis but also absorbed from milk. Evidence suggests that bovine milk exosomes contain microRNAs implicated in immune function. Feeding studies using a diet depleted of exosomes and their microRNA cargos showed changes in gene expression, metabolism, and phenotypes in mice. However, the role of milk exosomes and their microRNA cargos in inflammatory bowel disease is unknown. Previous studies focused on microRNA cargos in exosomes and disregarded mRNAs.The first chapter of this dissertation focuses on the role of bovine milk exosomes and their microRNA cargos in inflammatory bowel disease. Our findings demonstrate that depletion of dietary exosomes and microRNA cargos exacerbates signs of inflammatory bowel disease in Mdr1a-/- mouse model, in terms of more inflamed cecal tissues and higher cytokine concentration in serum. Consumption of an exosomes and microRNA cargos-depleted diet leads to a depletion of microRNAs in the tissue levels.The second chapter focuses on content of bovine mRNA cargos in milk exosomes, their bioavailability and potential in causing immune response. Results show that milk exosomes contain bovine mRNAs. The top expressed bovine mRNA in milk exosomes accumulate in liver tissues after oral gavage in mice. Even though the mRNA in milk exosomes contain AUT start codons, they are not translated into peptides. They are unlikely to cause immune responses when milk exosomes are used for delivery of therapeutic agents.The final chapter expands to microbial mRNA cargos in milk exosomes and their bioavailability. Almost half of the mRNA cargos in bovine milk exosomes, both from store-bought milk and raw milk origins, are non-bovine. Proteinase and RNase treatment provides evidence that these cargos are inside exosomes. A large portion of the non-bovine mRNA cargos are microbial mRNAs, and they are bioavailable in mice and humans.
Wu, Di, "Function and Metabolism of MRNA and MicroRNA Cargos in Bovine Milk Exosomes in Non-Bovine Mammals" (2021). ETD collection for University of Nebraska - Lincoln. AAI28419750.