Protective effects of miR‑155‑5p silencing on IFN‑γ‑induced apoptosis and inflammation in salivary gland epithelial cells

Experimental and Therapeutic Medicine, Год журнала: 2021, Номер 22(2)

Опубликована: Июнь 15, 2021

Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate miR‑155‑5p SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon‑γ (IFN‑γ). apoptosis SGECs measured using flow cytometry. Levels proinflammatory factors were detected reverse transcription‑quantitative PCR ELISA, respectively. Immunofluorescence used for p65 staining. Dual‑luciferase reporter assay performed verify interaction between arrestin β2 (ARRB2). protein levels NF‑κB signaling pathway assessed western blotting. results treatment IFN‑γ increased expression, addition inducing inflammation SGECs. Furthermore, overexpression promoted IFN‑γ‑induced Overexpression also Bax enzyme activities caspase 3 9, release cytokines interleukin‑6 tumor necrosis factor‑α, decreased Bcl‑2 expression IFN‑γ‑treated By contrast, all effects aforementioned reversed following knockdown. These activated pathway, where inhibitor, pyrrolidine dithiocarbamate, on target ARRB2 negatively regulated levels, such response, Collectively, from suggest may activate regulating promote damage during pathogenesis. This suggests be potential SS.

Язык: Английский

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Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations

Scientific Reports, Год журнала: 2021, Номер 11(1)

Опубликована: Май 27, 2021

Abstract Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary lacrimal glands. Although the etiology SS remains unclear, evidence suggests that epithelial damage glands elicits immune fibrotic responses in SS. To define molecular changes underlying tissue SS, we laser capture microdissected (LCM) labial gland epithelia from 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation gene expression signatures revealed that, addition to division samples, there was potential intermediate state overlapping clustering samples. Differential uncovered signaling events likely distinct pathogenesis. Notable signals included enrichment IFN-γ JAK/STAT-regulated genes, induction genes encoding secreted factors, such as LTF, BMP3, MMP7, implicated responses, matrix remodeling destruction. Identification mixed clinical histopathological characteristics pathology may be defined subtypes. We conclude arising damaged offer novel insights into contributing development progression.

Язык: Английский

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Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy

International Journal of Radiation Oncology*Biology*Physics, Год журнала: 2021, Номер 111(5), С. 1237 - 1249

Опубликована: Июль 16, 2021

PurposeSevere xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction radiation-related toxicity. The aim this study was to create an efficient prognostic miRNA-based test severe, patient-rated 3 months after primary treatment.Methods and MaterialsThis prospective enrolled with cancer treated between 2016 2018 centers Poland. endpoint severe (grade ≥3) assessed by European Organisation Research Treatment Cancer H&N-35 questionnaires. Initially, a group 10 randomly selected matched comparative without xerostomia. Samples were collected before radiation therapy, receiving 20 Gy, within 24 hours treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) used quantify expression levels 752 miRNAs serum at all timepoints. resulting logistic-regression based model validated additional 60 patients: 30 grade >3 without.ResultsOf 152 eligible patients, we successfully recruited 111 patients. Severe reported 63 (56.8%). Mean dose delivered parotid glands higher both exploratory validation cohort. on miR-185-5p miR-425-5p measured start therapy had area under curve 0.96 (95% confidence interval, 0.88-1.00). same remained robust when parameters Gy (area 0.90; 95% 0.75-1.00). These results confirmed group. In group, preradiation application yielded 73.3% sensitivity 80.0% specificity. samples taken 2 67.7% 72.4% including pretreatment together mean 90.0% cohort, 80.6% 55.2% miRNA 100% specificity cohort its performance fell 71.0% 58.6% specificity.ConclusionsSerum or during (after Gy) significant value occurrence variability explained appears be, least partially, independent from that related dosimetric data. treatment. This without. Of Serum

Язык: Английский

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RETRACTED ARTICLE: Mirt2 functions in synergy with miR-377 to participate in inflammatory pathophysiology of Sjögren's syndrome

Artificial Cells Nanomedicine and Biotechnology, Год журнала: 2019, Номер 47(1), С. 2473 - 2480

Опубликована: Июнь 14, 2019

Background The interaction of long non-coding RNAs (lncRNAs)-microRNAs (miRs) exerts crucial functions in mediating inflammatory reaction. It is still unclear whether myocardial infarction associated transcript 2 (Mirt2)-miR-377 mediates the pathogenesis Sjögren's syndrome (SS).Methods lesion model was established by stimulating salivary gland epithelial cells (SGECs) interferon gamma (IFN-γ). Mirt2- and/or miR-377-transfected SGECs, as well their negative controls, were applied to investigate biological inflammation. Cell viability and apoptosis examined using commercial kits. Western blot quantify protein level, enzyme-linked immuno sorbent assay (ELISA) used value secretion cytokines.Results up-regulation Mirt2 observed IFN-γ-treated SGECs. overexpression restored expression miR-377 which repressed IFN-γ. However, silence abolished protective effect on cell viability, inhibitory prohibitive role pro-inflammatory factors. diminished phosphorylated regulators while phosphorylation SGECs.Conclusion elevated SGECs then up-regulated response lesions. Mechanically, synergy with blocked IFN-γ-evoked activation NF-κB JAK/STAT signalling pathway.

Язык: Английский

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Exosome-Derived microRNAs from Mouthrinse Have the Potential to Be Novel Biomarkers for Sjögren Syndrome

Journal of Personalized Medicine, Год журнала: 2022, Номер 12(9), С. 1483 - 1483

Опубликована: Сен. 10, 2022

Sjögren syndrome (SS) is diagnosed based on invasive tissue biopsies and blood sampling. Therefore, a novel non-invasive simple inspection diagnostic marker of SS required. Here, we identified exosome-derived microRNAs (miRNAs) as biomarkers for using mouthrinse samples collected from patients with healthy volunteers. We compared miRNAs derived exosomes in the two groups microarrays real-time polymerase chain reaction (PCR) 12 biomarker candidates. The expression ratios four were significantly increased group to control group. Logistic regression analysis revealed more significant influence miR-1290 let-7b-5p than that combined these create prediction formula logistic analysis. combination distinguished an AUC, sensitivity, specificity, positive predictive value, negative value 0.856, 91.7%, 83.3%, 84.6%, 90.9%, respectively. These results indicated ratio could serve SS. This first report diagnosis screening by adopting method mouthrinse.

Язык: Английский

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