Redox-sensitive transcription factors play a significant role in the development of rheumatoid arthritis

2017 ◽  
Vol 37 (3) ◽  
pp. 129-143 ◽  
Author(s):  
Scott Le Rossignol ◽  
Natkunam Ketheesan ◽  
Nagaraja Haleagrahara
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Significant Role

scholarly journals Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases

2020 ◽  
Vol 21 (4) ◽  
pp. 1340 ◽  
Author(s):  
Riko Nishimura ◽  
Kenji Hata ◽  
Yoshifumi Takahata ◽  
Tomohiko Murakami ◽  
Eriko Nakamura ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Genetic Disorder ◽  
Interleukin 1 ◽  
Genetic Diseases ◽  
Mtor Inhibitors ◽  
Joint Diseases ◽  
Ectopic Ossification ◽  
Parathyroid Hormone Related Protein

Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases that globally affect more than 200 million and 20 million people, respectively. Several transcription factors have been implicated in the onset and progression of osteoarthritis, including Runx2, C/EBPβ, HIF2α, Sox4, and Sox11. Interleukin-1 β (IL-1β) leads to osteoarthritis through NF-ĸB, IκBζ, and the Zn2+-ZIP8-MTF1 axis. IL-1, IL-6, and tumor necrosis factor α (TNFα) play a major pathological role in rheumatoid arthritis through NF-ĸB and JAK/STAT pathways. Indeed, inhibitory reagents for IL-1, IL-6, and TNFα provide clinical benefits for rheumatoid arthritis patients. Several growth factors, such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), parathyroid hormone-related protein (PTHrP), and Indian hedgehog, play roles in regulating chondrocyte proliferation and differentiation. Disruption and excess of these signaling pathways cause genetic disorders in cartilage and skeletal tissues. Fibrodysplasia ossificans progressive, an autosomal genetic disorder characterized by ectopic ossification, is induced by mutant ACVR1. Mechanistic target of rapamycin kinase (mTOR) inhibitors can prevent ectopic ossification induced by ACVR1 mutations. C-type natriuretic peptide is currently the most promising therapy for achondroplasia and related autosomal genetic diseases that manifest severe dwarfism. In these ways, investigation of cartilage and chondrocyte diseases at molecular and cellular levels has enlightened the development of effective therapies. Thus, identification of signaling pathways and transcription factors implicated in these diseases is important.

scholarly journals Large-scale meta-analysis across East Asian and European populations updated genetic architecture and variant-driven biology of rheumatoid arthritis, identifying 11 novel susceptibility loci

2020 ◽  
pp. annrheumdis-2020-219065
Author(s):  
Eunji Ha ◽  
Sang-Cheol Bae ◽  
Kwangwoo Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
T Cell Activation ◽  
Fixed Effects ◽  
Genetic Architecture ◽  
Association Studies ◽  
Meta Analysis ◽  
Chromatin Interaction ◽  
Susceptibility Loci ◽  
European Populations

ObjectivesNearly 110 susceptibility loci for rheumatoid arthritis (RA) with modest effect sizes have been identified by population-based genetic association studies, suggesting a large number of undiscovered variants behind a highly polygenic genetic architecture of RA. Here, we performed the largest-ever trans-ancestral meta-analysis with the aim to identify new RA loci and to better understand RA biology underlying genetic associations.MethodsGenome-wide RA association summary statistics in three large case–control collections consisting of 311 292 individuals of Korean, Japanese and European populations were used in an inverse-variance-weighted fixed-effects meta-analysis. Several computational analyses using public omics resources were conducted to prioritise causal variants and genes, RA variant-implicating features (tissues, pathways and transcription factors) and potentially repurposable drugs for RA treatment.ResultsWe identified 11 new RA susceptibility loci that explained 6.9% and 1.8% of the single-nucleotide polymorphism-based heritability in East Asians and Europeans, respectively, and confirmed 71 known non-human leukocyte antigens (HLA) susceptibility loci, identifying 90 independent association signals. The RA variants were preferentially located in binding sites of various transcription factors and in cell type-specific transcription–activation histone marks that simultaneously highlighted the importance of CD4+ T-cell activation and the potential role of non-immune organs in RA pathogenesis. A total of 615 plausible effector genes, based on gene-based associations, expression-associated variants and chromatin interaction, included targets of drugs approved for RA treatments and potentially repurposable drugs approved for other indications.ConclusionOur findings provide useful insights regarding RA genetic aetiology and variant-driven RA pathogenesis.

scholarly journals REL, encoding a member of the NF-κB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis

2009 ◽  
Vol 41 (7) ◽  
pp. 820-823 ◽  
Author(s):  
Peter K Gregersen ◽  
Chistopher I Amos ◽  
Annette T Lee ◽  
Yue Lu ◽  
Elaine F Remmers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Risk Locus

scholarly journals Similarity and Potential Relation Between Periimplantitis and Rheumatoid Arthritis on Transcriptomic Level: Results of a Bioinformatics Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyi Li ◽  
Changqing Zhou ◽  
Yongqian Xu ◽  
Yujia Wang ◽  
Lijiao Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Feature Selection ◽  
Transcription Factors ◽  
Cross Talk ◽  
Differential Expression Analysis ◽  
Functional Enrichment ◽  
Support Vector ◽  
Bioinformatics Study ◽  
Control Samples

BackgroundThis bioinformatics study aimed to reveal potential cross-talk genes, related pathways, and transcription factors between periimplantitis and rheumatoid arthritis (RA).MethodsThe datasets GSE33774 (seven periimplantitis and eight control samples) and GSE106090 (six periimplantitis and six control samples) were included from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). A differential expression analysis (p < 0.05 and |logFC (fold change)| ≥ 1) and a functional enrichment analysis (p < 0.05) were performed. Based on this, a protein–protein interaction (PPI) network was constructed by Cytoscape. RA-related genes were extracted from DisGeNET database, and an overlap between periimplantitis-related genes and these RA-related genes was examined to identify potential cross-talk genes. Gene expression was merged between two datasets, and feature selection was performed by Recursive Feature Elimination (RFE) algorithm. For the feature selection cross-talk genes, support vector machine (SVM) models were constructed. The expression of these feature genes was determined from GSE93272 for RA. Finally, a network including cross-talk genes, related pathways, and transcription factors was constructed.ResultsPeriimplantitis datasets included 138 common differentially expressed genes (DEGs) including 101 up- and 37 downregulated DEGs. The PPI interwork of periimplantitis comprised 1,818 nodes and 2,517 edges. The RFE method selected six features, i.e., MERTK, CD14, MAPT, CCR1, C3AR1, and FCGR2B, which had the highest prediction. Out of these feature genes, CD14 and FCGR2B were most highly expressed in periimplantitis and RA. The final activated pathway–gene network contained 181 nodes and 360 edges. Nuclear factor (NF) kappa B signaling pathway and osteoclast differentiation were identified as potentially relevant pathways.ConclusionsThis current study revealed FCGR2B and CD14 as the most relevant potential cross-talk genes between RA and periimplantitis, which suggests a similarity between RA and periimplantitis and can serve as a theoretical basis for future research.

scholarly journals A significant role of transcription factors E2F in inflammation and tumorigenesis of nasopharyngeal carcinoma

2020 ◽  
Vol 524 (4) ◽  
pp. 816-824
Author(s):  
Peishan Liu ◽  
Xiaoyue Zhang ◽  
Zhengshuo Li ◽  
Lingyu Wei ◽  
Qiu Peng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Nasopharyngeal Carcinoma ◽  
Significant Role

scholarly journals Transcription Factor Assay of Peripheral Blood T cells in Different Groups of Rheumatoid Arthritis Patients

2020 ◽  
Vol 8 (4) ◽  
pp. 153-162
Author(s):  
Saeid Taghiloo ◽  
◽  
Abolghasem Ajami ◽  
Mohsen Tehrani ◽  
Arezou Abbasi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Peripheral Blood ◽  
Treg Cells ◽  
The Body ◽  
Th2 Cells ◽  
Healthy Controls ◽  
Relative Expression ◽  
Significant Difference

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and other tissues and organs of the body. Previous reports have demonstrated the imbalance of T helper (Th) subsets and Treg activity in the development, progression, and remission of RA. Here, we investigated the mRNA expression of four major transcription factors T-bet (Th1), GATA (Th2), RORc (Th17), and Foxp3 (Treg) in peripheral blood of different groups of RA patients. Materials and methods: In this case-control study, 60 patients with RA, including 20 newly diagnosed, 20 under treatment, and 20 in remission, as well as 20 patients with osteoarthritis, and 20 age- and the sex-matched healthy individual were enrolled. Diagnosis and classification of patients were done according to the American College of Rheumatology criteria. The relative mRNA expression of transcription factors, including T-bet, GATA, RORc, and Foxp3, was measured using qRT-PCR. Results: The relative expression of T-bet in RA patients was significantly increased in healthy controls (P = 0.002), while the relative expression of Foxp3 in RA patients was significantly decreased in healthy controls (P < 0.0001). There was no significant difference in the expression of GATA3 or RORc among RA patients, healthy controls, and osteoarthritis group. Conclusions: The results indicate the importance of Th1 and Treg cells in RA; however, the role of Th17 cells appear to be of little importance in these patients. It seems that Th2 cells do not interfere with RA development.

Sign in / Sign up

Export Citation Format

Share Document