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Gene & Protein in Disease                                 Exosomes connect periodontitis and systemic diseases



            which can directly merge with a preexisting ESE. The trans-  exosomes also enter serum, lymph and cerebrospinal fluid,
            Golgi network (TGN) and endoplasmic reticulum (ER)   breast  milk,  urine,  saliva,  and  other  body  fluids  to  play
            also can contribute to the formation and contents of ESE.   different biological roles [61,62] .
            ESEs can mature into late-sorting endosomes (LSEs), they   After released by parent cells, exosomes can navigate
            can become multivesicular bodies (MVBs) due to the LSEs
            accumulation. This process results in MVBs containing   through extracellular fluid for varying times and distances.
                         [55]
            several exosomes . MVBs can fuse with autophagosomes,   When exosomes reach the location of particular tissue,
            and the contents are degraded in the lysosomes ultimately,   they are internalized by recipient cells through receptor-
            MVBs can also directly fuse with lysosomes for     mediated endocytosis, pinocytosis, and phagocytosis, or
            degradation. The degradation products could be recycled   through the fusion with cell membrane, which results in
                                                                                               [63]
            by the cells . Besides, MVBs can be transported to plasma   direct release of contents into cytoplasm . The receptor-
                    [56]
            membrane and docked on the luminal side of plasma   mediated endocytosis plays a critical role during the
            membrane by the help of MVB-docking proteins to release   entry of exosomes into target cells. Exosomes can interact
            these exosomes [53,57] . Through the above process, cells can   with recognized specific target cells and then establish
            package cargoes consisting of selective lipids, proteins,   interactions with the surface of recipient cells by binding to
            and nucleic acids in exosomes, and such cargoes can be   their receptors or other appropriate sites, which is followed
            transported to recipient cells, contributing to expressional   by exosomes fusion with plasma membrane. After this
            and functional changes  (Figure 2).                process, exosomes can discharge the luminal cargoes into
                              [58]
                                                               the recipient cells, resulting  in the physiological change
            3.2. Uptake of exosomes                            of recipient cells. After that, exosomes components can
            As a kind of extracellular vesicles, exosomes can be released   be reassembled in new vesicles that are recycled by other
                                                                                           [16]
            from a variety of cells including fibroblasts, intestinal ECs,   cells to activate effector networks . Exosomes can also
            neurons, and adipocytes [59,60] . Exosomes tend to move   release contents into recipient cells by fusing with cells.
            through the intercellular junctions, leave their initial fluid   Subsequently, exosomes membranes and cargoes can
            and move to adjacent areas of tissues, and communicate   redistribute in the recipient cell, which can then be recycled
            with neighboring cells through cell-cell connections,   for MVBs or plasma membrane assembly, respectively.
            which is the primary function of exosomes. Meanwhile,   Recycled exosomes are released to the extracellular fluid






























            Figure 2. Biogenesis and uptake of exosomes. Exosomes are originated from the invagination of cell membranes containing special contents, which leads to
            the production of ESEs. Instantly, intracellular proteins and nucleic acids merged with ESEs to form LSEs, ER and TGN also can participate in this process.
            Eventually, LSEs mature into MVBs, which contain many newly formed exosomes and some of them will be excreted out of the body after being digested
            by autophagosomes or lysosomes, while others will be secreted out of donor cell as carriers. Along with the transport of body fluids, these exosomes can
            release contents into the recipient cells by fusion or endocytosis, causing physiological changes in the recipient cells. ESEs: Early-sorting endosomes, ER:
            Endoplasmic reticulum, TGN: Trans-Golgi network, LSEs: Late-sorting endosomes.


            Volume 1 Issue 2 (2022)                         4                       https://doi.org/10.36922/gpd.v1i2.99
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