Exosomes in Sepsis

Murao, Atsushi; Brenner, Max; Aziz, Monowar; Wang, Haichao

doi:10.3389/fimmu.2020.02140

Cited by 71 publications

(73 citation statements)

References 85 publications

(157 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…Exosomes, biological lipid bilayer nanoparticles secreted via the endosomal pathway of cells, have recently emerged as important cargos that carry multiple mediators critical for the pathogenesis of sepsis-associated organ dysfunctions [ 37 ]. Meanwhile, the application of exosomes in sepsis may be a novel approach for sepsis treatment [ 37 – 39 ]. Recently, circular RNAs have been identified for their enrichment and stability in exosomes, and exosomal circRNAs have potential applications as biomarkers and novel therapeutic targets in human diseases [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Knockdown of circ-FANCA alleviates LPS-induced HK2 cell injury via targeting miR-93-5p/OXSR1 axis in septic acute kidney injury

Li¹,

Zhang

Wang

et al. 2021

Diabetol Metab Syndr

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Background Sepsis is life-threatening disease with systemic inflammation and can lead to various diseases, including septic acute kidney injury (AKI). Recently, diverse circular RNAs (circRNAs) are considered to be involved in the development of this disease. In this study, we aimed to elucidate the role of circ-FANCA and the potential action mechanism in sepsis-induced AKI. Methods HK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. The expression of circ-FANCA, microRNA-93-5p (miR-93-5p) and oxidative stress responsive 1 (OXSR1) mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. The inflammatory response was monitored according to the release of pro-inflammatory cytokines via enzyme-linked immunosorbent assay (ELISA). The activities of oxidative indicators were examined using the corresponding kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the interaction between miR-93-5p and circ-FANCA or OXSR1. Protein analysis was conducted through western blot. Results Circ-FANCA was upregulated in septic AKI serum specimens and LPS-treated HK2 cells. Functionally, circ-FANCA knockdown facilitated cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-triggered HK2 cells. Further mechanism analysis revealed that miR-93-5p was a target of circ-FANCA and circ-FANCA modulated LPS-induced cell damage by targeting miR-93-5p. Meanwhile, miR-93-5p overexpression repressed LPS-treated HK2 cell injury by sponging OXSR1. Furthermore, circ-FANCA regulated OXSR1 expression by sponging miR-93-5p. Besides, exosome-derived circ-FANCA was upregulated in LPS-induced HK2 cells, which was downregulated by GW4869. Conclusion Circ-FANCA knockdown attenuated LPS-induced HK2 cell injury by regulating OXSR1 expression via targeting miR-93-5p.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockdown of circ-FANCA alleviates LPS-induced HK2 cell injury via targeting miR-93-5p/OXSR1 axis in septic acute kidney injury

Li¹,

Zhang

Wang

et al. 2021

Diabetol Metab Syndr

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“…The constitution of gut microbiome is altered by sepsis, which may contribute to organ dysfunction [ 51 , 52 ]. S-EVs are thought to be capable of eliciting inflammation by delivering cytokines or damage-associated molecular pattern to target tissues [ 53 ]. In accordance with these notions one can consider that the EVs secreted during sepsis may reshape contents of gut microbiota by direct or indirect transfer of their biologically active contents including pro-inflammatory mediators or miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation

Appiah

Park

Darkwah

et al. 2020

IJMS

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Sepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis mice and patients to either promote or suppress inflammation. Little is known about how the gut epithelial cell-derived exosomes released in the intestinal luminal space during sepsis affect mucosal inflammation. To study this question, we isolated extracellular vesicles (EVs) from intestinal lavage of septic mice. The EVs expressed typical exosomal (CD63 and CD9) and epithelial (EpCAM) markers, which were further increased by sepsis. Moreover, septic-EV injection into inflamed gut induced a significant reduction in the messaging of pro-inflammatory cytokines TNF-α and IL-17A. MicroRNA (miRNA) profiling and reverse transcription and quantitative polymerase chain reaction (RT-qPCR) revealed a sepsis-induced exosomal increase in multiple miRNAs, which putatively target TNF-α and IL-17A. These results imply that intestinal epithelial cell (IEC)-derived luminal EVs carry miRNAs that mitigate pro-inflammatory responses. Taken together, our study proposes a novel mechanism by which IEC EVs released during sepsis transfer regulatory miRNAs to cells, possibly contributing to the amelioration of gut inflammation.

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“…In systemic lupus erythematosus it was observed that EVs expressed pro-inflammatory immune complexes [ 58 ]. In term of sepsis, there are also several data regarding the contribution of the EVs [ 59 ]. Platelet-derived EVs of septic patients were shown to induce apoptosis in endothelial cells and cardiomyocytes that lead to vascular dysfunctions and cardiomyopathy [ 60 ].…”

Section: Introductionmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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Similar to other cell types, neutrophilic granulocytes also release extracellular vesicles (EVs), mainly medium-sized microvesicles/microparticles. According to published data, authors have reached a consensus on the physical parameters (size, density) and chemical composition (surface proteins, proteomics) of neutrophil-derived EVs. In contrast, there is large diversity and even controversy in the reported functional properties. Part of the discrepancy may be ascribed to differences in the viability of the starting cells, in eliciting factors, in separation techniques and in storage conditions. However, the most recent data from our laboratory prove that the same population of neutrophils is able to generate EVs with different functional properties, transmitting pro-inflammatory or anti-inflammatory effects on neighboring cells. Previously we have shown that Mac-1 integrin is a key factor that switches anti-inflammatory EV generation into pro-inflammatory and antibacterial EV production. This paper reviews current knowledge on the functional alterations initiated by neutrophil-derived EVs, listing their effects according to the triggering agents and target cells. We summarize the presence of neutrophil-derived EVs in pathological processes and their perspectives in diagnostics and therapy. Finally, the functional heterogeneity of differently triggered EVs indicates that neutrophils are capable of producing a broad spectrum of EVs, depending on the environmental conditions prevailing at the time of EV genesis.

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Exosomes in Sepsis

Cited by 71 publications

References 85 publications

Knockdown of circ-FANCA alleviates LPS-induced HK2 cell injury via targeting miR-93-5p/OXSR1 axis in septic acute kidney injury

Knockdown of circ-FANCA alleviates LPS-induced HK2 cell injury via targeting miR-93-5p/OXSR1 axis in septic acute kidney injury

Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

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