A Next-Generation Sequencing of Plasma Exosome-Derived microRNAs and Target Gene Analysis with a Microarray Database of Thermally Injured Skins: Identification of Blood-to-Tissue Interactions at Early Burn Stage

Abstract

Background Plasma exosome-derived microRNA (miRNA) profiles following thermal injury and their relationship with gene expression derangements in burned skin remain unexplored. This study focused on the identification of key miRNA-mRNA axes in potential blood-to-tissue interactions at early burn stage. Methods Plasma exosomes were obtained from 6 severe burn patients 4–7 days post injury and 6 healthy volunteers. Next-generation sequencing (NGS) of exosomal small RNAs presented the differentially expressed miRNAs (DEMs). Target genes of the DEMs were predicted in the mirDIP database. Dataset GSE8056 was enrolled to acquire differentially expressed genes (DEGs) in burned skin compared to normal skin. Overlap between the DEGs and target genes of the DEMs were focus genes. The protein–protein interaction (PPI) network and enrichment analyses of the focus genes demonstrated hub genes and suggested underlying mechanisms and pathways. The hub genes and upstream DEMs were selected to construct key miRNA-mRNA axes. Results The NGS of plasma exosome-derived small RNAs identified 85 DEMs (14 downregulated miRNAs and 71 upregulated miRNAs) with 12,901 predicted target genes. Dataset GSE8056 exhibited 1861 DEGs in partial-thickness burned skins 4–7 days postburn. The overlap between DEGs and target genes of DEMs displayed 1058 focus genes. The top 9 hub genes (CDK1, CCNB1, CCNA2, BUB1B, PLK1, KIF11, AURKA, NUSAP1 and CDCA8) in the PPI network of the focus genes pointed to 16 upstream miRNAs in DEMs, including 4 downregulated miRNAs (hsa-miR-6848-3p, has-miR-4684-3p, has-miR-4786-5p and has-miR-365a-5p) and 12 upregulated miRNAs (hsa-miR-6751-3p, hsa-miR-718, hsa-miR-4754, hsa-miR-6754-3p, hsa-miR-4739, hsa-miR-6739-5p, hsa-miR-6884-3p, hsa-miR-1224-3p, hsa-miR-6878-3p, hsa-miR-6795-3p, hsa-miR-550a-3p, and hsa-miR-550b-3p). A key miRNA-mRNA network in potential blood-to-tissue interactions at early burn stage was therefore constructed. Conclusion An NGS and bioinformatic analysis in the study identified key miRNA-mRNA axes in potential blood-to-tissue interactions at early burn stage, suggesting plasma exosome-derived miRNAs may impact on the alteration patterns of gene expressions in a burn wound.

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“…Together with the in vivo result, these observations indicated an intercellular communication between microglia and neurons. In the past few years, exosomes carrying proteins, miRNAs and other bioactive substances have been widely regarded as a transporter for intercellular signal transduction (Li et al., 2021; Zhou et al., 2020). miRNAs can be encapsulated by exosomes and freely cross the blood–brain barrier, and therefore this is a potential strategy to target the RVLM region through this pathway without brainstem injections, which would increase translatability into clinical practice.…”

Exosomes and Their Bioengineering Strategies in the Cutaneous Wound Healing and Related Complications: Current Knowledge and Future Perspectives

“…Furthermore, compared to local damage caused by mechanical injury, the permeability of burns has a systemic effect on the body. RNA-sequencing-based studies have found that plasma exosome-derived microRNA profiles are altered after thermal injury, which may be an important cause of disordered skin gene expression in the early burn stage 168 , 169 . Protein profiling-based studies have found that burns induce significant changes in serum exosomal protein function, altering enzyme inhibitor activity, heparin-binding, coagulation, and lipid transport 170 .…”