MicroRNA-sequencing Analysis of Plasma-derived Exosomes Provides Novel Insights into the Disease Mechanism of Childhood Atopic Dermatitis

Abstract

Background: Exosomes are nano-size vesicles that plays important roles in transporting cellular modulators including microRNAs (miRNAs), DNA and proteins between cells. Exosomes and their components are proved to implicate a variety of dermatologic disorders in adults. However, the expression pattern of exosomal miRNAs in pediatric atopic dermatitis (AD) patients has not been well studied. Methods: Plasma samples were drawn from 5 pediatric AD patients and 5 age-matched healthy volunteers. Small RNA sequencing was performed to identify differentially expressed exosomal miRNAs (DEPEMs) between those two groups. Bioinformatics tools including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to explore the DEPEMs involved canonical pathways and their relationships with the pathogenesis of AD. Reverse transcription real-time polymerase chain reaction (RT-qPCR) was used for validation and measurement of DEPEM levels. Results: A total of 40 DEPEMs, including 29 upregulated and 11 downregulated DEPEMs, were identified. Using the miRanda and TargetScan databases, 17,238 target genes of the 40 DEPEMs were predicted. GO and KEGG pathway enrichment analyses suggested that these target genes were involved in multiple functions and pathways associated with AD, such as the skin barrier, T-cell differentiation and keratinocyte proliferation. 10 selected DEPEMS, including 5 downregulated miRNAs (hsa-miR-1343-3p, hsa-miR-301a-5p_R-1, hsa-mir-1273c-p3, hsa-miR-374b-3p and hsa-miR-1908-5p) and 5 upregulated miRNAs (hsa-let-7b-3p_R-1_1ss21CT, hsa-miR-34a-5p, hsa-miR-100-5p_R-1, hsa-miR-27a-5p and hsa-mir-3976-p3_1ss16AT) were verified through RT-qPCR. Conclusions: This study provides the first genomic profile for understanding the pathogenesis and potential biomarkers for pediatric AD patients. The DEPEMs from our study differs from those from adult AD patients, suggesting children with AD have distinct peripheral exosomal miRNA expression. DEPEMs may serve as promising novel biomarkers or regulators of pediatric AD pathology.