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.

Extracellular Vesicles in the Pathogenesis, Clinical Characterization, and Management of Dermatomyositis: A Narrative Review

“…Two other studies additionally identified RNA profiles from DM EVs, one study focusing on miRNAs from neutrophil-derived EVs and the other on those from plasmaderived EVs. The former study identified that a total of 32 miRNAs were differentially expressed in DM patients compared to healthy controls, 17 of which were upregulated and 15 were downregulated [21]. Gene ontology analysis suggested that these miRNA target genes participate in actin filament organization, endothelial cell development and differentiation, and muscle tissue development [21].…”

“…Understanding how EVs may be contributing to the proinflammatory response in DM helps in determining the mechanisms behind the vasculopathy, muscle damage, and skin lesions that characterize this disease. Another important aspect of EVs in DM concerns their clinical applications, whereby EVs have shown potential for use as biomarkers in diagnosis, classification of subtypes, and management [7,8,[14][15][16][17][18][19][20][21].…”

Idiopathic inflammatory myopathy and non-coding RNA

“…The clinical features of IIMs are accompanied by a significant inflammatory response, muscle volume loss, and multiple histological findings ( 14 ). NcRNAs changes in the inflammatory response and muscle atrophy also confirm this finding.…”

“…Genetic ontological analysis of differentially expressed lncRNAs and mirRNAs showed that they produce IL-6 and IFN-β and promote the proliferation and development of skeletal muscle cells. KEGG analysis indicated that the autophagic pathway, PI3K-Akt, and AMP-activated protein kinase (AMPK) signaling pathways are involved in DM pathogenesis ( 14 ). Another histological study showed that the miRNAs in the EXO of patients with DM were involved in its pathogenesis.…”

MicroRNAs in idiopathic inflammatory myopathies: state-of-the-art and future perspectives

“…Among studies attesting the serum level of miR-NAs in dermatomyositis patients, Li et al [79] identified 32 differentially expressed miRNAs from neutrophil-derived EVs whose target genes were involved in actin filament organization, muscle tissue development, endothelial cell development, and differentiation. Interestingly, let-7b, miR-3907, and miR-4299 in sera of patients with dermatomyositis have been associated with disease activity [80], whereas miR-125a-3p, miR-1246, and miR-3614-5p correlated with muscle enzymes, organ involvement, and positivity for myositis-specific antibodies.…”