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      Downregulated Serum Exosomal miR-451a Expression Correlates With Renal Damage and Its Intercellular Communication Role in Systemic Lupus Erythematosus

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          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.

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          Most cited references58

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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            Exosomes: composition, biogenesis and function

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              Exosomes

              Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                12 February 2021
                2021
                : 12
                : 630112
                Affiliations
                [1] 1Department of Dermatology, Third Xiangya Hospital, Central South University , Changsha, China
                [2] 2Department of Dermatology, Second Xiangya Hospital, Central South University , Changsha, China
                [3] 3Xiangya School of Medicine, Central South University , Changsha, China
                Author notes

                Edited by: Kutty Selva Nandakumar, Southern Medical University, China

                Reviewed by: Constantino Martinez, University of Murcia, Spain; Nattiya Hirankarn, Chulalongkorn University, Thailand; Rujuan Dai, Virginia Tech, United States

                *Correspondence: Jinrong Zeng zengjinrong1989@ 123456csu.edu.cn

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.630112
                7906989
                33643314
                9a188e2d-e4bf-44ad-90e1-7b3a57c9ef63
                Copyright © 2021 Tan, Zhao, Wu, Zhang, Tong, Gao, Zhou, Lu and Zeng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 November 2020
                : 22 January 2021
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 58, Pages: 14, Words: 7981
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Natural Science Foundation of Hunan Province 10.13039/501100004735
                Categories
                Immunology
                Original Research

                Immunology
                exosome,microrna-451a,serum,renal damage,sle
                Immunology
                exosome, microrna-451a, serum, renal damage, sle

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