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      Extracellular Vesicles as an Endocrine Mechanism Connecting Distant Cells

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          Abstract

          The field of extracellular vesicles (EVs) has expanded tremendously over the last decade. The role of cell-to-cell communication in neighboring or distant cells has been increasingly ascribed to EVs generated by various cells. Initially, EVs were thought to a means of cellular debris or disposal system of unwanted cellular materials that provided an alternative to autolysis in lysosomes. Intercellular exchange of information has been considered to be achieved by well-known systems such as hormones, cytokines, and nervous networks. However, most research in this field has searched for and found evidence to support paracrine or endocrine roles of EV, which inevitably leads to a new concept that EVs are synthesized to achieve their paracrine or endocrine purposes. Here, we attempted to verify the endocrine role of EV production and their contents, such as RNAs and bioactive proteins, from the regulation of biogenesis, secretion, and action mechanisms while discussing the current technical limitations. It will also be important to discuss how blood EV concentrations are regulated as if EVs are humoral endocrine machinery.

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          Most cited references94

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          Shedding light on the cell biology of extracellular vesicles

          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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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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              Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

              In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
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                Author and article information

                Journal
                Mol Cells
                Mol Cells
                Molecules and Cells
                Korean Society for Molecular and Cellular Biology
                1016-8478
                0219-1032
                30 November 2022
                3 November 2022
                3 November 2022
                : 45
                : 11
                : 771-780
                Affiliations
                [1 ]Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
                [2 ]Adipose Management, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
                Author notes
                Author information
                https://orcid.org/0000-0002-8937-0053
                https://orcid.org/0000-0002-0851-9603
                Article
                molce-45-11-771
                10.14348/molcells.2022.0110
                9676990
                36380729
                0557391b-0db2-4d3c-bc23-1ba5ce40663d
                © The Korean Society for Molecular and Cellular Biology. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 5 July 2022
                : 1 August 2022
                : 15 August 2022
                Categories
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                adiponectin,ceramide,exosome,extracellular vesicles,syntenin,tetraspanin

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