Exosomes, 40-100 nm sized extracellular vesicles, are enriched in endosome-derived components. 1,2 Exosomes can be secreted by almost all types of cells such as fibroblasts, macrophages, tumor cells, and mesenchymal stem cells, and they can be found in amniotic fluid, milk, urine, ascites fluid, blood, cerebrospinal fluid, and even saliva. 3,4 Exosomes were first discovered in mature mammalian reticulocytes by Johnstone in 1987. 5 After decades of researches, scientists have discovered that exosomes have unique structures. First, exosomes are mostly "cup-shaped" or "circular," with a density of 1.13-1.19 g/ml. 3 Second, membranes of exosomes are rich in lipid rafts, cholesterol, sphingomyelins, and ceramides and have a variety of transmembrane proteins on its surface. Third, as an endogenous vector, exosomes contain functional proteins, mRNAs, and microR-NAs (miRNAs), DNAs and other signaling molecules. 6,7 Fourth, surface proteins and other related receptors of exosomes can reflect specific biological sources, for instance, CD9, CD63, and CD81. 8 With the gradual understanding of exosomes, their functions have gone from "junk" to "supernova". 9 The reasons are as follows:Foremost, in the body's immune response, exosomes are responsible for antigen presentation, stimulation of T-cell proliferation, and activation of immune response. 10 Next, miRNAs carried by exosomes can be used as biomarkers for the early diagnosis and prognosis of diseases, for instance, breast cancer, colorectal cancer, and prostate cancer. [11][12][13] Furthermore, because of the absence of cellular structure, exosomes are considered as ideal biological drug delivery
The biological mechanism underlying the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In this study, we found 21 proteins upregulated and 38 proteins downregulated by SLE relative to normal protein metabolism in our samples using liquid chromatography-mass spectrometry. By PPI network analysis, we identified 9 key proteins of SLE, including AHSG, VWF, IGF1, ORM2, ORM1, SERPINA1, IGF2, IGFBP3, and LEP. In addition, we identified 4569 differentially expressed metabolites in SLE sera, including 1145 reduced metabolites and 3424 induced metabolites. Bioinformatics analysis showed that protein alterations in SLE were associated with modulation of multiple immune pathways, TP53 signaling, and AMPK signaling. In addition, we found altered metabolites associated with valine, leucine, and isoleucine biosynthesis; one carbon pool by folate; tyrosine metabolism; arginine and proline metabolism; glycine, serine, and threonine metabolism; limonene and pinene degradation; tryptophan metabolism; caffeine metabolism; vitamin B6 metabolism. We also constructed differently expressed protein-metabolite network to reveal the interaction among differently expressed proteins and metabolites in SLE. A total of 481 proteins and 327 metabolites were included in this network. Although the role of altered metabolites and proteins in the diagnosis and therapy of SLE needs to be further investigated, the present study may provide new insights into the role of metabolites in SLE.
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