T cell exosome–derived miR-142-3p impairs glandular cell function in Sjögren’s syndrome

JCI Insight, Год журнала: 2020, Номер 5(9)

Опубликована: Май 6, 2020

Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine salivary and lacrimal glands. Local inflammation in the glands thought to trigger glandular dysfunction symptoms of dryness. However, mechanisms underlying these processes are incompletely understood. Our work suggests T cell exosome–derived miR-142-3p as pathogenic driver immunopathology SS. We first document expression patients with SS, both epithelial gland cells within inflammatory infiltrate, but not healthy volunteers. Next, we show activated secreted exosomes containing miR-142-3p, which transferred into cells. Finally, uncover functional role miR-142-3p–containing dysfunction. find targets key elements intracellular Ca2+ signaling cAMP production — sarco(endo)plasmic reticulum ATPase 2b (SERCA2B), ryanodine receptor 2 (RyR2), adenylate cyclase 9 (AC9) leading restricted production, altered calcium signaling, decreased protein from provides evidence for SS pathogenesis promotes concept activation may directly impair function through secretion miRNA-containing exosomes.

Язык: Английский

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The Spectrum of Extraglandular Manifestations in Primary Sjögren’s Syndrome

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(6), С. 961 - 961

Опубликована: Июнь 7, 2023

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of systemic involvement this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees dysfunction. The existing gaps knowledge complex domain extraglandular extension pSS need to overcome order increase diagnostic accuracy pSS. timely identification EGMs, as early from subclinical stages, facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on criteria for range pSS, which associates important underdiagnosing subsequent undertreatment progression dysfunction these patients. This review article presents most recent basic science research conducted investigate pathogenic mechanisms leading In addition, it current treatment recommendations trends future therapeutic strategies based personalized treatment, well latest field prognostic biomarkers

Язык: Английский

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The Role of Deregulated MicroRNAs in Immune Cells of Sjögren’s Disease

International Journal of General Medicine, Год журнала: 2025, Номер Volume 18, С. 847 - 855

Опубликована: Фев. 1, 2025

The 2024 Nobel Prize in Physiology or Medicine, awarded for the discovery of microRNAs (miRNAs) as essential regulators gene expression, has spotlighted their pivotal roles disease processes, including autoimmune conditions such Sjögren's (SD). SD is a chronic marked by lymphocytic infiltration exocrine glands, resulting significant glandular dysfunction and diverse systemic effects. Recent research revealed that miRNAs play crucial pathogenesis, orchestrating immune cell activity, epithelial integrity, regulation inflammatory pathways. Dysregulation specific associated with exacerbated responses, damage, dysfunction, sustained inflammation, positioning these small RNA molecules central players progression. This review synthesizes current findings on SD, highlighting how certain contribute to dysregulation, chronicity. Additionally, we explore potential biomarkers reflecting both health, novel therapeutic targets. By consolidating recent advancements, aim offer comprehensive perspective involvement underscore miRNA-based strategies transform diagnosis, management, treatment SD.

Язык: Английский

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Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome

Arthritis Research & Therapy, Год журнала: 2020, Номер 22(1)

Опубликована: Июнь 22, 2020

Abstract Background The aim of this study was to identify the molecular mechanism dysregulation B cell subpopulations primary Sjögren’s syndrome (pSS) at transcriptome level. Methods We enrolled patients with pSS ( n = 6) and healthy controls (HCs) in discovery cohort using microarray 14) HCs 12) validation quantitative PCR (qPCR). Peripheral cells acquired from these subjects were separated by sorting into four subsets: CD38 − IgD + (Bm1), (naive cells), high (pre-germinal centre cells) ± (memory cells). performed differentially expressed gene (DEG) analysis weighted co-expression network (WGCNA). Results Expression long non-coding RNA LINC00487 significantly upregulated all subsets, as that HLA interferon (IFN) signature genes. Moreover, normalized intensity value correlated disease activity score subsets. Studies human lines revealed expression strongly induced IFNα. WGCNA six clusters associated subpopulation pSS. Further, SOX4 identified an inter-module hub gene. Conclusion Our key genes involved Trial registration Not required.

Язык: Английский

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Ophthalmologic Manifestations of Primary Sjögren’s Syndrome

Genes, Год журнала: 2021, Номер 12(3), С. 365 - 365

Опубликована: Март 4, 2021

Sjögren’s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially lacrimal and salivary, with their consequent destruction. The onset primary SS (pSS) may remain misunderstood for several years. It usually presents different types severity, e.g., dry eye mouth symptoms, due to early involvement salivary which be associated parotid enlargement eye; keratoconjunctivitis sicca (KCS) its most common ocular manifestation. still doubtful if extent surface manifestations are secondary or meibomian gland targeting corneal conjunctival autoantigens. representative cause aqueous deficient eye, role inflammatory process was evidenced. Recent scientific progress in understanding numerous factors involved pathogenesis pSS registered, but exact mechanisms need clarified. unquestionable both innate adaptive immune system, participating actively induction evolution recognized. inflammation central mechanism leading decrease secretion keratoconjunctival alterations. However, there controversies about whether direct target gland. In this review, we aimed present actual knowledge relative pSS, considering immunity, genetics.

Язык: Английский

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Association of endometriosis with Sjögren's syndrome: Genetic insights (Review)

International Journal of Molecular Medicine, Год журнала: 2024, Номер 53(2)

Опубликована: Янв. 3, 2024

Patients with a history of endometriosis have an increased risk developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is potential association between susceptibility for Sjögren's syndrome (SS). SS common chronic, inflammatory, systemic, autoimmune, multifactorial disease complex pathology, genetic, epigenetic environmental factors contributing to the development this condition. It occurs in 0.5‑1% population, characterized by presence ocular dryness, lymphocytic infiltrations contributes neurological, gastrointestinal, vascular dermatological manifestations. Endometriosis estrogen‑dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% reproductive‑age women. occurrence endometrial tissue outside uterine cavity, mainly pelvic associated pain, dysmenorrhea, deep dyspareunia either subfertility or infertility. still unclear whether appears secondary response endometriosis, it developed due any shared mechanisms these conditions. The aim present review was explore further biological basis only co‑occurrence disorders but not their at clinical basis, focusing on analysis partially genetic background SS, clarification possible similarities underlying pathogenetic relevant molecular pathways.

Язык: Английский

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miR-216a-3p alleviates primary Sjögren's syndrome by regulating the STAT1/JAK signaling pathway

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер unknown, С. 151647 - 151647

Опубликована: Март 1, 2025

Язык: Английский

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Long Non-Coding RNAs Modulate Sjögren’s Syndrome Associated Gene Expression and Are Involved in the Pathogenesis of the Disease

Journal of Clinical Medicine, Год журнала: 2019, Номер 8(9), С. 1349 - 1349

Опубликована: Сен. 1, 2019

Primary Sjögren’s syndrome (pSjS) is a chronic systemic autoimmune disorder, primarily affecting exocrine glands; its pathogenesis still unclear. Long non-coding RNAs (lncRNAs) are thought to play role in the of diseases and comprehensive analysis lncRNAs expression pSjS lacking. To this aim, more than 540,000 human transcripts, including those ascribed 50,000 profiled at same time, cohort 16 peripheral blood mononuclear cells PBMCs samples (eight eight healthy subjects). A complex network carried out on global set molecular interactions among modulated genes lncRNAs, leading identification reliable lncRNA-miRNA-gene functional interactions. Taking approach, few identified as targeting highly connected transcriptome, since they have major impact gene modulation disease. Such involved biological processes pathways crucial pSjS, immune response, B cell development function, inflammation, apoptosis, type I gamma interferon, epithelial adhesion polarization. The deregulated that modulate typical features disease provides insight opens avenues for design novel therapeutic strategies.

Язык: Английский

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SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(6), С. 3203 - 3203

Опубликована: Март 21, 2021

There is considerable interest in delineating the molecular mechanisms of action transforming growth factor-β (TGF-β), considered as central player a plethora human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, regulate transcription target genes collaboration with various co-activators co-repressors. Until now, therapeutic strategy for primary Sjögren's syndrome (pSS) has been focused on inflammation, but, recently, involvement TGF-β/SMADs demonstrated pSS salivary glands (SGs) mediator epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause SG fibrosis, family members have ambiguous function SGs. Based these premises, this review highlights recent advances unravelling basis multi-faceted functions that are dictated by orchestrations describe value both disease markers and/or pSS.

Язык: Английский

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Deletion of miR-146a enhances therapeutic protein restoration in model of dystrophin exon skipping

Molecular Therapy — Nucleic Acids, Год журнала: 2024, Номер 35(3), С. 102228 - 102228

Опубликована: Май 24, 2024

Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the absence of dystrophin protein. One current DMD therapeutic strategy, exon skipping, produces truncated isoform using phosphorodiamidate morpholino oligomers (PMOs). However, potential skipping therapeutics has not been fully realized as increases in protein have minimal clinical trials. Here, we investigate how miR-146a-5p, which highly elevated dystrophic muscle, impacts levels. We find inflammation strongly induces miR-146a dystrophic, but wild-type myotubes. Bioinformatics analysis reveals that 3' UTR harbors binding site, and subsequent luciferase assays demonstrate inhibits translation. In dystrophin-null

Язык: Английский

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