Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis

Kim, Jimin; Lee, Seul Ki; Jeong, Seon-Yeong; Cho, Hye Jin; Park, Joonghoon; Kim, Tae Min; Kim, Soo Jeong

doi:10.1186/s12951-021-01120-y

Cited by 20 publications

(21 citation statements)

References 83 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When amoebae were co-incubated with neutrophils (1:100), it was interesting to observe the release of EVs smaller than 100 nm that had not been observed in separate cultures, and that could constitute typical exosomes. Variation not only in size, but also in cargo, is a well-known characteristic of EVs obtained under different culture conditions, stimuli, and even exposure times ( Tiruvayipati et al., 2020 ; Kim et al., 2021 ). Here, we found that under coculture conditions EVs from amoebae and neutrophils tend to aggregate.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils

Díaz-Godínez

Ríos-Valencia

García-Aguirre

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Parasites release extracellular vesicles (EVs) which, in some cases, modulate the host’s immune response contributing to the establishment of the infection. In this work we have isolated and characterized the EVs released by trophozoites of the human protozoan parasite Entamoeba histolytica, the causal agent of amoebiasis, when alone or in coculture with human neutrophils, and determined their effect on neutrophil NETs and ROS production. Nanoparticle tracking analysis showed that amoebic EVs are variable in size, ranging from less than 50 nm to nearly 600 nm in diameter (average of 167 nm), whereas neutrophil EVs are more uniform in size, with an average of 136 nm. In cocultures amoeba:neutrophil (1:100) most EVs are 98 nm in size, which is the typical size of exosomes. EVs from amoebae and neutrophils showed almost equal levels of ROS, which were considerably increased in EVs from cocultures. Uptake of amoebic EVs by neutrophils was demonstrated by fluorescence and resulted in a significant reduction in the oxidative burst and NET release triggered by PMA, ionophore A23187, or the amoebae itself used as stimuli. Interestingly, uptake of EVs from cocultures did not affect ROS production, but instead caused a greater delay in the onset of NETs release and in their quantity. A comparative proteomic analysis between the EVs of amoebae and neutrophils separately vs the cocultures showed a similar distribution of protein categories in the GO analysis, but differences in the expression and abundance of proteins such as the N-acetyl-D-galactosamine (GalNAc) inhibitable surface lectin and calreticulin in amoeba EVs, and various antimicrobial molecules in neutrophil EVs, such as lactoferrin and myeloperoxidase. These results highlight the importance of EVs in the immunomodulatory effects exerted by amoeba on human neutrophils.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils

Díaz-Godínez

Ríos-Valencia

García-Aguirre

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…For measurement of mRNA expression, total RNA was isolated, and real-time qPCR was performed, as described previously [ 80 ]. The primer sequences are listed in Additional file 1 : Table S7.…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice

Kim¹,

Lee²,

Jung³

et al. 2022

J Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. Results Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. Conclusions IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.

show abstract

“…A recent study demonstrated that the infusion of c-kit-positive liver sinusoidal endothelial cells (LSECs) improves homeostasis in the pericentral liver endothelium and diet-induced NASH in mice by impacting LSEC–macrophage–neutrophil crosstalk mediated by repressing C-X-C motif chemokine receptor 4 (CXCR4) transcription by CCAAT enhancer-binding protein α (CEBPA) ( Duan et al, 2022 ). In addition to cell implantation, EVs from pan-PPAR agonist-stimulated-induced mesenchymal stem cell (pan PPAR-iMSC-EVs) can facilitate NASH progression, contributing to ameliorating hepatic steatosis, ER stress, oxidative stress, and apoptosis ( Kim et al, 2021a ). MSC-derived apoptotic vesicles have significant potential in the treatment of NASH, considering macrophage regulatory effects and efferocytosis mediated by calreticulin ( Zheng et al, 2021 ).…”

Section: Stem Cell-based Therapy In Nashmentioning

confidence: 99%

Current, emerging, and potential therapies for non-alcoholic steatohepatitis

Yang

Wang

2023

Front. Pharmacol.

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) has been identified as the most common chronic liver disease worldwide, with a growing incidence. NAFLD is considered the hepatic manifestation of a metabolic syndrome that emerges from multiple factors (e.g., oxidative stress, metabolic disorders, endoplasmic reticulum stress, cell death, and inflammation). Non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, has been reported to be a leading cause of cirrhosis and hepatic carcinoma, and it is progressing rapidly. Since there is no approved pharmacotherapy for NASH, a considerable number of therapeutic targets have emerged with the deepening of the research on NASH pathogenesis. In this study, the therapeutic potential and properties of regulating metabolism, the gut microbiome, antioxidant, microRNA, inhibiting apoptosis, targeting ferroptosis, and stem cell-based therapy in NASH are reviewed and evaluated. Since the single-drug treatment of NASH is affected by individual heterogeneous responses and side effects, it is imperative to precisely carry out targeted therapy with low toxicity. Lastly, targeted therapeutic agent delivery based on exosomes is proposed in this study, such that drugs with different mechanisms can be incorporated to generate high-efficiency and low-toxicity individualized medicine.

show abstract

Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis

Cited by 20 publications

References 83 publications

Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils

Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils

Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice

Current, emerging, and potential therapies for non-alcoholic steatohepatitis

Contact Info

Product

Resources

About