Exosomes Derived from Mouse Adipose-Derived Mesenchymal Stem Cells Alleviate Benzalkonium Chloride-Induced Mouse Dry Eye Model via Inhibiting NLRP3 Inflammasome

Ophthalmic Research, Год журнала: 2021, Номер 65(1), С. 40 - 51

Опубликована: Сен. 16, 2021

The objective of the study was to investigate efficacy and mechanisms mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in benzalkonium chloride (BAC)-induced dry eye model.Exosomes mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, transmission electron microscopy used characterize mADSC-Exos. An experimental model established instillation 0.2% BAC. mADSC-Exos administered following BAC treatment. positive control group treated with commercial drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, film break-up time (BUT) evaluated, histologic analysis cornea conjunctiva performed hematoxylin eosin periodic acid-Schiff staining. Apoptosis corneal epithelium detected terminal deoxynucleotidyl transferase dUTP nick-end labeling assay blotting. Levels pro-inflammatory cytokines evaluated flow cytometry, mRNA protein levels NLR family pyrin domain-containing 3 (NLRP3) pathway components assessed quantitative real-time PCR respectively.mADSC-Exos characterized as vesicles a bilayer membrane. particle size distribution peak at 134 nm. specifically expressed cluster differentiation (CD)9, CD63, CD81. treatment repaired ocular surface damage. Additionally, inhibited cell apoptosis, decreased interleukin (IL)-1β, IL-6, IL-1α, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, increased anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation upregulation caspase-1, IL-1β, IL-18 reversed mADSC-Exos.mADSC-Exos alleviate inflammation, suggesting that it is promising for eye.

Язык: Английский

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An Overview of the Dry Eye Disease in Sjögren’s Syndrome Using Our Current Molecular Understanding

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1580 - 1580

Опубликована: Янв. 13, 2023

Sjögren's syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye other systemic manifestations. However, due the high prevalence lack objective clinically reliable diagnostic tools, discriminating (SSDE) from non-Sjögren's (NSSDE) remains challenge for clinicians. Diagnosing SS important improve quality life through timely referral workups, as associated serious complications such lymphoma autoimmune diseases. purpose this article describe current molecular understanding its implications novel modalities on horizon. A literature review pre-clinical clinical studies published between 2016 2022 was conducted. SSDE pathophysiology immunology pathways have become better understood in recent years. Novel modalities, tear saliva proteomics well exosomal biomarkers, provide hope

Язык: Английский

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Tear Film MicroRNAs as Potential Biomarkers: A Review

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3694 - 3694

Опубликована: Фев. 12, 2023

MicroRNAs are non-coding RNAs that serve as regulatory molecules in a variety of pathways such inflammation, metabolism, homeostasis, cell machinery, and development. With the progression sequencing methods modern bioinformatics tools, novel roles microRNAs mechanisms pathophysiological states continue to expand. Advances detection have further enabled larger adoption studies utilizing minimal sample volumes, allowing analysis low-volume biofluids, aqueous humor tear fluid. The reported abundance extracellular these biofluids has prompted explore their biomarker potential. This review compiles current literature reporting human fluid association with ocular diseases including dry eye disease, Sjögren’s syndrome, keratitis, vernal keratoconjunctivitis, glaucoma, diabetic macular edema, retinopathy, well non-ocular diseases, Alzheimer’s breast cancer. We also summarize known shed light on future this field.

Язык: Английский

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miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июнь 6, 2023

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate role and mechanisms tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in pathogenesis HT.Differentially expressed sEV miRNAs were identified between HT normal RNA sequencing testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays logistic regression analysis validation 60), most relevant verified. parental recipient cells miRNA then explored. In vitro vivo experiments further performed function potential contribute development HT.We miR-142-3p encapsulated T lymphocyte-derived sEVs can induce Treg defect destruction through intact response loop. Inactivation effectively protect non-obese diabetic (NOD).H-2h4 mice from display reduced infiltration, lower antibody titers, higher Looking at underlying action on destruction, we found strong deleterious effect mediated due its ability block activation ERK1/2 signaling pathway downregulating RAC1.Our findings highlight fact sEV-mediated transfer serve as a communication mode lymphocytes HT, favoring progression HT.

Язык: Английский

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Exosomes, extracellular vesicles and the eye

Experimental Eye Research, Год журнала: 2021, Номер 214, С. 108892 - 108892

Опубликована: Дек. 10, 2021

Язык: Английский

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Recent Advances in the Use of Exosomes in Sjögren’s Syndrome

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Авг. 6, 2020

Sjögren's syndrome (SS) is a chronic autoimmune disorder of exocrine glands mediated by lymphocytic infiltrates damaging the body tissues and affecting life quality patients. Although traditional methods diagnosis treatment for SS are effective, in time personalized medicine, new biomarkers novel approaches required detection SS. Exosomes represent an emerging field discovery management Exosomes, subtype extracellular vesicles, secreted various cell types can be found most bodily fluids. packed with cytokines other proteins, bioactive lipids, nucleic acids (mRNA, circular RNA, non-coding tRNA, microRNA, genomic DNA, ssDNA), transport such cargo between cells. Evidence has indicated that exosomes may play roles processes as modulation immune response activation inflammation. Moreover, due to features stability, low immunogenicity toxicity, long half-life, capacity penetrate blood-brain barrier, have also emerged therapeutic tools In this review, we summarize existing literature regarding biogenesis, isolation, function exosomes, specifically focusing on their potential uses

Язык: Английский

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Promising Roles of Exosomal microRNAs in Systemic Lupus Erythematosus

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Дек. 13, 2021

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the loss of immune tolerance. Lupus nephritis (LN) still major cause morbidity and mortality SLE. In clinical practice, diagnosis, therapy SLE complicated challenging due to lack ideal biomarkers. Exosomes could be detected from numerous kinds biological fluids their specific contents are considered as hallmarks diseases. The exosomal miRNA profiles SLE/LN patients significantly differ those healthy controls making them attractive biomarkers for renal injury. optimal delivery vehicles owing higher stable, minimal toxicity, lower immunogenicity features target effects. Endogenous miRNAs can functionally transferred exosomes donor cells recipient cells, displaying immunomodulatory addition, it has been confirmed that directly interact with Toll-like receptors (TLRs) signaling pathways regulate NF-κB activation secretion inflammatory cytokines. present Review mainly focuses on effects exosomal-miRNAs, complex interplay between exosomes, TLR pathways, how exosomal-miRNAs become non-invasive diagnostic molecules potential therapeutic strategies management

Язык: Английский

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Research status and future prospects of extracellular vesicles in primary Sjögren’s syndrome

Stem Cell Research & Therapy, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 3, 2022

Abstract Primary Sjögren’s syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation T B lymphocytes, infiltration lymphocytes. With development modern medicine, although research on pathogenesis, diagnosis, treatment pSS has made significant progress, its pathogenesis not been fully understood. Meanwhile, in era individualized treatment, it remains essential to further explore early diagnosis methods. Exosomes, small vesicles containing proteins nucleic acids, are subtype extracellular secreted various cells present body fluids. Exosomes contribute variety biological functions, including intercellular signal transduction pathophysiological processes, may play role immune tolerance. Therefore, exosomes key understanding diseases. can also be used therapeutic tool for because their biodegradability, low immunogenicity toxicity, ability bypass blood–brain barrier, implying prospect broad application context pSS. Here, we systematically review isolation, identification, tracing, mode action vesicles, especially exosomes, well progress

Язык: Английский

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Extracellular vesicles derived from CD4+ T cells carry DGKK to promote sepsis-induced lung injury by regulating oxidative stress and inflammation

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Март 23, 2023

Abstract Background Sepsis is an abnormal immune response after infection, wherein the lung most susceptible organ to fail, leading acute injury. To overcome limitations of current therapeutic strategies and develop more specific treatment, inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. Methods Liquid chromatography–tandem mass spectrometry was performed for serum EV protein profiling. The diacylglycerol kinase kappa (DGKK) endotoxin contents patients with sepsis-induced injury were measured. Apoptosis, oxidative stress, inflammation A549 cells, bronchoalveolar lavage fluid, tissues mice measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot. Results DGKK, key regulator (DAG)/protein C (PKC) pathway, exhibited elevated expression EVs showed strong correlation sepsis severity disease progression. DGKK expressed CD4 + cells under regulation NF-κB pathway delivered target including alveolar epithelial cells. produced lymphocytes exerted toxic effects on induce apoptotic cell death, damage, inflammation. In induced cecal ligation puncture, derived from also promoted tissue lungs. These attenuated inhibition PKC NOX4, downstream effectors DAG. Conclusions This approach established mechanism that T-cell-derived carrying triggered apoptosis, inflammation, damage through DAG/PKC/NOX4 pathway. Thus, distribution further investigated

Язык: Английский

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Salivary Exosomes in Health and Disease: Future Prospects in the Eye

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6363 - 6363

Опубликована: Март 28, 2023

Exosomes are a group of vesicles that package and transport DNA, RNA, proteins, lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, ocular have been reported, but not fully unraveled. The exosomes saliva less studied, offer significant advantages over sources, due their accessibility ease collection. Thus, role in the pathophysiology diseases is largely unknown. In context salivary under-utilized, thus creating an enormous gap literature. current review discusses state research systemic highlights potential future therapeutic vehicles.

Язык: Английский

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