Page 112 - GPD-1-2

Gene & Protein in Disease Exosomes connect periodontitis and systemic diseases

by the previous target cell, which becomes the parent can also affect cell survival, especially changing the levels
cell eventually [61,64] . Another process that does not occur of components essential for the control of cell migration,
frequently is that exosomes directly recognize the cell development and metastasis .
[75]
surface receptors, which is not followed by exosome fusion
but results in the activation of intracellular signaling . 3.4. Physiological and pathophysiological functions
[65]
of exosomes
3.3. Composition and main contents in exosomes
The function of exosomes depends on the status of original
The contents of exosomes mirror the composition of donor cells or tissues at the stage of exosome generation .
[61]
cells; therefore, they contain various kinds of constituents Exosomes can regulate many pathophysiological
due to diverse cell origin, including lipids, cytosolic and processes including immune responses, inflammation,
[57]
cell-surface proteins, metabolites, DNA, RNA, and so on . tumor growth, and infections . As mediators of cell-
[71]
Lipids in exosomes are not only involved in the formation cell communication, exosomes play a crucial role in
of exosome, but also play an irreplaceable influence in the maintenance of cells, homeostasis and regulation of
the physiological and pathological processes of cells. As cellular functions. Exosomes are involved in the recycling
mentioned above, lipids and lipid-metabolizing enzymes of cell surface proteins and signaling molecules to affect
are involved in the formation and release of exosomes . cell proliferation, differentiation, and apoptosis through
[66]
On the one hand, exosomes are formed by lipid bilayer paracrine pathways. Meanwhile, exosomes as cellular
membrane, and released by cells after fusion of MVBs with garbage bags can expel excess and nonfunctional cellular
the plasma membrane. Although the molecular mechanism components to maintain normal cellular functions [61,64] .
of this process is still unclear, a study has already shown In the inflammatory responses, exosomal cargos, such
that glycosphingolipids can be involved in the release as interferon alpha, can suppress the infection effects
[67]
of exosomes . On the other hand, exosomes contain by limiting viral replication or enhancing antiviral
lots of other lipids, including cholesterol, sphingolipid, immunity . Similarly, exosomes can regulate the function
[18]
sphingomyelin, phosphatidylserine, arachidonic acid, and of immune cells which mediate immune responses. Some
other fatty acids; prostaglandins and leukotrienes in these studies have shown that exosomes derived from antigen
fatty acids can be utilized as inflammation biomarkers . presenting cells, such as dendritic cells, can express MHC
[18]
Exosomes also include some specific proteins and Classes I and II molecules and costimulatory signals on
non-specific proteins. Specific proteins include integrins, the cells surface to present the peptide antigen to specific T
tetraspanins, major histocompatibility complex (MHC) cells directly to induce their activation which contributes
Class I, II, and so on. Among these proteins, tetraspanins to the induction of specific immune responses [76,77] .
can assemble into functionally active membrane structures
together with other transmembrane proteins . Moreover, 3.5. Different isolation methods of exosomes
[68]
CD63 and CD81 are recognized as specific markers of There are different methods for separating exosomes based
exosomes . A range of fusion and transferring proteins on their size, shape, flotation density, and labeled protein.
[69]
such as Rab2, Rab7, flotillin, and annexin, heat shock Exosomes can be isolated by using ultracentrifugation,
proteins (HSP) such as HSP70 and HSP90, cytoskeleton density gradient centrifugation, ultrafiltration, precipitation,
proteins such as actin, myosin and tubulin, and proteins and immunoaffinity capture from conditioned media or
that mediate MVBs formation such as Alix belong to non- body fluids . However, each method has its advantages
[78]
specific protein types in exosomes . The nucleic acids and disadvantages as shown in Table 1.
[70]
contained in exosomes include mRNA, miRNA as well as
long non-coding RNA, cyclic DNA, and so on . Some 4. The role of exosomes in periodontitis
[71]
studies have proven that nucleic acids in exosomes are Exosomes are associated with a variety of inflammatory
involved in many diseases, such as tumors, cardiovascular diseases, and they can be treated as vehicles to transfer
diseases, and autoimmune diseases [69,72] . MiRNAs perform inclusions from donor cells to target cells and influence
negative regulation and confer characteristic changes their metabolism . Exosomes secreted by human
[18]
in the expression levels of target genes . Interestingly,
[73]
some miRNAs were found to have novel functions when periodontal ligament stem cells (PDLSCs) are a kind vesicle
they are in exosomes. Exosomal miR-21 and miR-29a, containing lipids, proteins, mRNAs, and non-coding
in addition to the classic role of targeting mRNA, were RNAs, all of them are important during the intercellular
communications and periodontitis occurrence .
[85]
first discovered to have the capacity to act as ligands that
bind to toll-like receptors (TLRs) and activate immune While invading periodontal tissues, pathogenic factors
cells . Furthermore, miRNAs in the upstream of mRNA stimulate the production of exosomes in periodontal
[74]
Volume 1 Issue 2 (2022) 5 https://doi.org/10.36922/gpd.v1i2.99