Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

Comprehensive overview of microRNA function in rheumatoid arthritis

“…The delivery of miR-204-5p to RA-FLSs repressed cell activation, proliferation, and invasion as well as inflammatory cytokine production. 229 MiR-132 was found to be packaged into exosomes produced by Th17 cells and released into osteoclast precursors to promote their differentiation into mature osteoclasts via COX2 downregulation. Interestingly, cigarette smoke (CS) can act as an important agonist for AHR, and AHR signaling can result in further forced expression of miR-132 in patients with RA.…”

“… 254 Moreover, an inverse correlation between the levels of circulating exosomal miR-204-5p and ESR, CRP, and RF but not DAS28 and ACPA was noted recently. 229 …”

Macrophage-derived hybrid exosome-mimic nanovesicles loaded with black phosphorus for multimodal rheumatoid arthritis therapy

“…The proliferation, invading and cytokine secretion of synovial fibroblasts at the articular cavity is an important pathogenic factor for RA. 42 Here, L929 cells, a fibroblast cell line derived from a clone of normal subcutaneous areolar and adipose tissue in a male C3H/An mouse, 27 were taken as a model cell line to study the photothermal/photodynamic therapy (PTT/PDT) effect of the combination of HNV@BP and NIR irradiation on inflammatory cell viability. As shown in Fig.…”

Exosome application in treatment and diagnosis of B-cell disorders: leukemias, multiple sclerosis, and arthritis rheumatoid

“…human T lymphocytes also, can release exosomes containing numerous amounts of miR-204-5p which can be transferred into synovial fibroblasts and inhibit cell proliferation. Exosomal miR-204-5p expression is inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein [180].…”