scholarly journals SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3203
Author(s):  
Margherita Sisto ◽  
Domenico Ribatti ◽  
Sabrina Lisi
Keyword(s):  
Sjögren’S Syndrome ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Sjögren's Syndrome ◽  
Biological Effects ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mesenchymal Transition ◽  
Sjögren‘S Syndrome

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

scholarly journals Salivary transforming growth factor alpha in patients with Sjögren's syndrome and reflux laryngitis

2014 ◽  
Vol 80 (6) ◽  
pp. 462-469 ◽  
Author(s):  
Marco Antonio dos Anjos Corvo ◽  
Claudia Alessandra Eckley ◽  
Luis Vicente Rizzo ◽  
Luiz Roberto Sardinha ◽  
Tomas Navarro Rodriguez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sjögren’S Syndrome ◽  
Transforming Growth Factor ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Transforming Growth Factor Alpha ◽  
Reflux Laryngitis ◽  
Factor Alpha ◽  
Sjögren‘S Syndrome

scholarly journals Mechanism of Dark Plum In Treatment of Sjögren's Syndrome Based On Network Pharmacology And Molecular Docking​

2021 ◽  
Author(s):  
Zhongli Sun ◽  
Lilin Deng ◽  
Zhoujie Xu ◽  
Kun Yang ◽  
Penglong Yu
Keyword(s):  
Molecular Docking ◽  
Sjögren’S Syndrome ◽  
Molecular Mechanisms ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Components ◽  
Sjögren‘S Syndrome

Abstract Background: Modern medicine has no cure for the xerostomia caused by the early onset of Sjögren's syndrome (SS).Dark plum is a common Chinese herbal medicine used to relieve xerostomia. However, the molecular mechanisms of the effects of dark plum are unknown. In this study, network pharmacology and molecular docking were used to investigate the mechanisms of action of dark plum on SS.Materials and method: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database was used to identify the active components and targets of dark plum, and the UniProt database was used to identify the genes encoding these targets. SS-related targets were also identified from the GeneCards and OMIM databases. By finding the intersection of the targets of the compounds and the targets of SS, the predicted targets of dark plum in the treatment of SS were obtained. Further investigation of the active compounds and their targets was carried out by constructing a network of "medicine-candidate compound-target-disease" using Cytoscape 3.7.2, the Protein-Protein Interaction(PPI) network using the STRING database and Cytoscape 3.7.2, and key targets were identified by Gene Ontology( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on R software. Finally, molecular docking was used to verify the affinity of the candidate compounds to the key targets.Results: Quercetin, beta-sitosterol, and kaempferol in dark plum interact with AKT1, IL-6, IL-1B, JUN, CASP3, and MAPK8. These results suggest that dark plum exerts its therapeutic effects on the peripheral gland injury of SS and its secondary cardiovascular disease and tumorigenesis through anti-inflammatory, anti-oxidant, and anti-tumor pathways.Conclusion: With network pharmacology, this study systematically identified the main active components, targets, and specific mechanisms of the therapeutic effects of dark plum on SS, providing both a theoretical basis and research direction for further investigations on dark plum.

scholarly journals Cytokines in Sjögren's syndrome: potential therapeutic targets

2010 ◽  
Vol 69 (6) ◽  
pp. 945-948 ◽  
Author(s):  
Nienke Roescher ◽  
Paul P Tak ◽  
Gabor G Illei
Keyword(s):  
Sjögren’S Syndrome ◽  
Inflammatory Cytokines ◽  
Low Dose ◽  
Sjögren's Syndrome ◽  
Biological Effects ◽  
Controlled Trial ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Early Results ◽  
Sjögren‘S Syndrome

The dysregulated cytokine network in Sjögren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low dose interferon (IFN) α showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal randomised controlled trial. Similarly, neither of the two tumour necrosis factor (TNF)-α blockers tested (etanercept and infliximab) showed efficacy in placebo controlled trials. Although the rationale for low dose oral IFN treatment has not been firmly established, TNF blockade was based on solid preclinical data. Therefore, the reason for the lack of efficacy is unclear, but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this. Cytokines, given their central role in the pathogenesis of SS, remain attractive targets for future treatments, despite the disappointing early results. Inflammatory cytokines are obvious candidates, and agents against several of them are available or under development for other autoimmune diseases similar to SS. New candidate cytokines such as IL-17 and IL-12 and/or IL-23 may provide promising targets for SS. Additionally, as an alternative to systemic treatment, which has the risk of potentially severe side effects, the use of local cytokine directed therapy should be explored.

The association of Raynaud’s phenomenon/syndrome with scleroderma and Sjögren’s syndrome – a meta-analysis

VASA ◽  
2008 ◽  
Vol 37 (Supplement 73) ◽  
pp. 26-32 ◽  
Author(s):  
Schlattmann ◽  
Höhne ◽  
Plümper ◽  
Heidrich
Keyword(s):  
Quantitative Analysis ◽  
Sjögren’S Syndrome ◽  
Mixture Model ◽  
Sjögren's Syndrome ◽  
Meta Analysis ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Raynaud’S Syndrome ◽  
Raynaud's Syndrome ◽  
Sjögren‘S Syndrome

Background: In order to analyze the prevalence of Raynaud’s syndrome in diseases such as scleroderma and Sjögren’s syndrom – a meta-analysis of published data was performed. Methods: The PubMed data base of the National Library of Medicine was used for studies dealing with Raynaud’s syndrome and scleroderma or Raynaud’s syndroem and Sjögren’s syndrom respectively. The studies found provided data sufficient to estimate the prevalence of Raynaud’s syndrome. The statistical analysis was based on methods for a fixed effects meta-analysis and finite mixture model for proportions. Results: For scleroderma a pooled prevalence of 80.9% and 95% CI (0.78, 0.83) was obtained. A mixture model analysis found four latent classes. We identified a class with a very low prevalence of 11%, weighted with 0.15. On the other hand there is a class with a very high prevalence of 96%. Analysing the association with Sjögren’s syndrome, the pooled analysis leads to a prevalence of Raynaud’s syndrome of 32%, 95% CI(26.7%, 37.7%). A mixture model finds a solution with two latent classes. Here, 38% of the studies show a prevalence of 18.8% whereas 62% observe a prevalence of 38.3%. Conclusion: There is strong variability of studies reporting the prevalence of Raynaud’s syndrome in patients suffering from scleroderma or Sjögren’s syndrome. The available data are insufficient to perform a proper quantitative analysis of the association of Raynaud’s phenomenon with scleroderma or Sjögren’s syndrome. Properly planned and reported epidemiological studies are needed in order to perform a thorough quantitative analysis of risk factors for Raynaud’s syndrome.

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