DNA methylation alterations in the pathogenesis of lupus

Chen, Shu‐Hui; Lv, Qiao‐Li; Hu, Lei; Wang, Gui‐Hua; Sun, Bao

doi:10.1111/cei.12877

Cited by 29 publications

(16 citation statements)

References 91 publications

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“…36 In particular, the up-regulation of miR-21, miR-29b, miR-30a, miR-126 and miR-148a and the down-regulation of miR-142-3p/5p and miR146a, positively correlate with DNA methylation changes occurring in CD4 + T cells, which are responsible for their marked autoreactivity, one of the hallmarks occurring in SLE. 37 In this work, we show a marked and significant up-regulation of some of them, such as miR-21, miR-195, miR-214 and miR-320a, and a significant down-regulation of miR-98 in SLE-derived hiPSCs compared to healthy hiPSCs-L ( Figure 4A), confirming the findings reviewed by Shen et al 36 Subsequently, we analysed a panel of oxidative stress-respon-…”

Section: The Protective Effects Of Ascorbic Acid In Hydrogen Peroxisupporting

confidence: 88%

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus

Angelis

Santamaria

Parrotta

et al. 2019

J Cellular Molecular Medi

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Involvement of the central nervous system (CNS) is an uncommon feature in systemic lupus erythematosus (SLE), making diagnosis rather difficult and challenging due to the poor specificity of neuropathic symptoms and neurological symptoms. In this work, we used human‐induced pluripotent stem cells (hiPSCs) derived from CNS‐SLE patient, with the aim to dissect the molecular insights underlying the disease by gene expression analysis and modulation of implicated pathways. CNS‐SLE‐derived hiPSCs allowed us to provide evidence of Erk and Akt pathways involvement and to identify a novel cohort of potential biomarkers, namely CHCHD2, IDO1, S100A10, EPHA4 and LEFTY1, never reported so far. We further extended the study analysing a panel of oxidative stress‐related miRNAs and demonstrated, under normal or stress conditions, a strong dysregulation of several miRNAs in CNS‐SLE‐derived compared to control hiPSCs. In conclusion, we provide evidence that iPSCs reprogrammed from CNS‐SLE patient are a powerful useful tool to investigate the molecular mechanisms underlying the disease and to eventually develop innovative therapeutic approaches.

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Section: The Protective Effects Of Ascorbic Acid In Hydrogen Peroxisupporting

confidence: 88%

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus

Angelis

Santamaria

Parrotta

et al. 2019

J Cellular Molecular Medi

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“…24,25 As methylation of CpG dinucleotides is a widely accepted phenomenon occurring during the immune response, attention recently has focused on the role of epigenetic alterations in the development of autoimmune disease. [26][27][28][29] A growing body of literature has demonstrated the relationship between impaired T-cell DNA methylation and some forms of autoimmune disease. [30][31][32][33] A significant hypomethylation of T-cell DNA has been demonstrated in patients with active systematic lupus erythematosus (SLE) and rheumatoid arthritis (RA), suggesting that T-cell mediated autoimmunity contributes to the pathogenesis of these diseases.…”

mentioning

confidence: 99%

Promoter Hypermethylation of GATA3, IL-4, and TGF-β Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han Chinese

Zhu

Qiu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We investigated the role of promoter methylation of transcriptional and inflammatory factors, including TBX21, GATA3, RORct, FOXP3, IFN-c, IL-4, IL-17A, and TGF-b in the development of Vogt-Koyanagi-Harada (VKH) disease. METHODS.The promoter methylation levels were detected by the Sequenom MassARRAY system in CD4 þ T cells that were separated from 20 healthy individuals and 32 VKH patients (20 in the active stage without medication, 12 in inactive stage with medication). The mRNA expression level of GATA3, IL-4, and TGF-b in CD4 þ T cells was analyzed by real-time RT-PCR. RESULTS.The promoter methylation levels of GATA3, IL-4, and TGF-b were significantly higher in active VKH patients than in healthy individuals (P < 0.05). A decreased mRNA expression of GATA3 and TGF-b was found in active VKH patients, which was correlated negatively with the DNA methylation of these factors. Treatment with systemic corticosteroid and cyclosporin A (CsA) decreased the methylation level of GATA3 and TGF-b in association with an increased mRNA expression of molecules and reduced disease activity. CONCLUSIONS. Our findings suggest that promoter hypermethylation of GATA3 and TGF-b in CD4þ T cells confers risk to VKH disease in Han Chinese.

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“…DNA hypomethylation and DNMT expression in lupus peripheral blood CD4 + T cells can be regulated by MAPKs, GADD45α, PP2A, and RFX1 [63,66,74]. Recent data indicate that ultraviolet B exposure reduced DNA methylation by inhibiting DNMT1 activity, suggesting that UV light might decrease methylation and increase expression of genes associated with SLE [75,76].…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%