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Surgical trauma in mice modifies the content of circulating extracellular vesicles

ABSTRACT: Purpose: Aseptic tissue injuries including major surgeries are associated with structural and functional changes in the brain suggesting the existence of periphery-to-brain communication. However, the nature of the carriers of such signaling remains largely unknown. Analyzis of the miRNAome and proteome of circulating extracellular vesicles (EVs) to evaluate their potential contribution to the periphery-to-brain signaling. Methods: EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, using Exoquick ULTRA commercial ki. Proteome and miRNAome were mapped using mass spectrometry and RNA-seq approaches. Results: Next-generation sequencing of small RNA libraries prepared from the total RNA isolated from the mouse serum EVs detected 252 miRNAs. Differential expression analysis using DESeq2 statistical package revealed 50 dysregulated miRNAs in the 24 h post-surgery EVs. The surgery effect declines after 72 h as judged by the lower number of dysregulated miRNAs. The differentially expressed miRNAs were examined by the DIANA-miRPath online tool that predicted dysregulation of several KEGG pathways including pathways involved in the lipid metabolism, ECM-receptor interaction, gap junction, various signal transduction pathways. Conclusions: The main question of the current project, is the surgery capable of modifying the expression of cargo molecules in circulating EVs, can be answered positively. Moreover, differential expression of a specific set of miRNAs in the “surgical” EVs suggests that they can be involved in the regulation of several metabolic pathways, such as ECM-receptor interaction and lipid metabolism in the recipient tissues, which is consistent with our data on hippocampal metabolic and functional dysregulation after surgery We conclude that surgery alters the EV composition in the blood, which paves the way for further studies on the functional effects of these EVs on the brain.

ORGANISM(S): Mus musculus

PROVIDER: GSE189972 | GEO | 2022/01/08

REPOSITORIES: GEO

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Surgical trauma in mice modifies the content of circulating extracellular vesicles

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