Abstract
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune-induced diffuse connective tissue disorder associated with immune inflammation, which involves multiple systems and organs, and leads to significant morbidity and mortality [1, 2]
Western blotting and Transmission Electron Microscopy (TEM) were used to validate the effectiveness of the serum exosome extraction technique applied
The TEM results indicated that the exosomes extracted from the serum samples exhibited a spherical structure, with a size range of 30–110 nm (Figure 1A), a feature that was similar to those reported previously [12, 25]
Summary
Systemic lupus erythematosus (SLE) is an autoimmune-induced diffuse connective tissue disorder associated with immune inflammation, which involves multiple systems and organs, and leads to significant morbidity and mortality [1, 2]. Serological biomarkers are crucial for achieving timely diagnosis and precise evaluation of SLE [3]. Recent studies have identified several new biomarkers that can be useful in clinical applications. MicroRNAs (miRNAs or miRs), exosomes and exosomal miRNAs can all serve as biomarkers in autoimmune diseases [4]. Published evidence indicates that miRNAs participate in different immune responses [5, 6], Role of miR-451a in SLE which makes them crucial candidates for use as diagnostic markers and treatment targets [7, 8]. Increasing evidence suggests that the expression characteristics of serum miRNAs makes them possible biomarkers of autoimmune diseases, including SLE, and they should be exploited for the betterment of humankind [9, 10]
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