The Functional Roles of RNAs Cargoes Released by Neutrophil-Derived Exosomes in Dermatomyositis

Abstract

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by cutaneous manifestations. We first identified the profiles of noncoding RNAs (lncRNAs and miRNAs) in peripheral neutrophil exosomes (EXOs) of DM patients and explored their potential functional roles. Bioinformatics analyses were performed with R packages. Real-time quantitative PCR was used to validate the altered RNAs in DM neutrophil EXO-stimulated human dermal microvascular endothelial cells (HDMECs) and human skeletal muscle myoblasts (HSkMCs). In DM neutrophil EXOs, 124 upregulated lncRNAs (with 1,392 target genes), 255 downregulated lncRNAs (with 1867 target genes), 17 upregulated miRNAs (with 2,908 target genes), and 15 downregulated miRNAs (with 2,176 target genes) were identified. GO analysis showed that the differentially expressed (DE) lncRNAs and DE miRNAs participated in interleukin-6 and interferon-beta production, skeletal muscle cell proliferation and development, and endothelial cell development and differentiation. KEGG analysis suggested that DE lncRNAs and DE miRNAs were enriched in the PI3K-Akt, MAPK, AMPK and FoxO signalling pathways. Many novel and valuable DE lncRNAs and DE miRNAs interacted and cotargeted in the PI3K-Akt, MAPK, AMPK and FoxO signalling pathways. Our study suggests that neutrophil EXOs participate in DM pathogenesis through lncRNAs and miRNAs in the PI3K-Akt, MAPK, AMPK and FoxO signalling pathways.

Keywords: AMPK; FoxO; MAPK; PI3K-Akt; dermatomyositis; lncRNA; miRNA; neutrophil-derived exosome.

FIGURE 1

Expression levels of DE lncRNAs (A) and DE miRNAs (B) in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways validated by real-time quantitative PCR in neutrophils of DM patients and in HDMECs and HSkMCs after stimulation with DM neutrophil EXOs (*DM vs. NC).