scholarly journals Epigenetic Contribution and Genomic Imprinting Dlk1-Dio3 miRNAs in Systemic Lupus Erythematosus

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 680
Author(s):  
Rujuan Dai ◽  
Zhuang Wang ◽  
S. Ansar Ahmed
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Methylation Status ◽  
Transcriptional Level ◽  
Dna Hypomethylation ◽  
Systemic Lupus ◽  
Multiple Organs ◽  
Genetic Imprinting

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that afflicts multiple organs, especially kidneys and joints. In addition to genetic predisposition, it is now evident that DNA methylation and microRNAs (miRNAs), the two major epigenetic modifications, are critically involved in the pathogenesis of SLE. DNA methylation regulates promoter accessibility and gene expression at the transcriptional level by adding a methyl group to 5′ cytosine within a CpG dinucleotide. Extensive evidence now supports the importance of DNA hypomethylation in SLE etiology. miRNAs are small, non-protein coding RNAs that play a critical role in the regulation of genome expression. Various studies have identified the signature lupus-related miRNAs and their functional contribution to lupus incidence and progression. In this review, the mutual interaction between DNA methylation and miRNAs regulation in SLE is discussed. Some lupus-associated miRNAs regulate DNA methylation status by targeting the DNA methylation enzymes or methylation pathway-related proteins. On the other hand, DNA hyper- and hypo-methylation are linked with dysregulated miRNAs expression in lupus. Further, we specifically discuss the genetic imprinting Dlk1-Dio3 miRNAs that are subjected to DNA methylation regulation and are dysregulated in several autoimmune diseases, including SLE.

scholarly journals Circular RNA circLOC101928570 Suppress Systemic Lupus Erythematosus Progression Via Targeting the miR-150/c-myb Axis

2021 ◽  
Author(s):  
Xingwang Zhao ◽  
Longlong Zhang ◽  
Juan Wang ◽  
Zhiqiang Song ◽  
Bing Ni ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transcriptional Level ◽  
Systemic Lupus ◽  
Potential Biomarker ◽  
Repressive Effect

Abstract Background: Accumulating evidence supports the implication of circRNAs in systemic lupus erythematosus (SLE). however, little is known about their the detailed mechanisms and the roles of circRNAs in the pathogenesis of SLE.Methods: Quantitative real time-PCR (qRT-PCR) was used to determine the levels of circLOC101928570 and miR-150 in peripheral blood mononuclear cells (PBMCs) of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), luciferase reporter assays, western blot, flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate the molecular mechanisms underlying the function of circLOC101928570. Results: The results showed that the level of circLOC101928570 was significantly down-regulated in SLE and correlated with systemic lupus erythematosus disease activity index (SLEDAI). Functionally, circLOC101928570 acted as a miR-150 sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promote the transcriptional level of IL2RA through directly regulate miR-150/c-myb axis. Conclusion: Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The down-expression of circLOC101928570 suppressed SLE progression through miR-150/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serve as a potential biomarker for the diagnosis and therapy of SLE.

Critical role of DNA methylation in the pathogenesis of systemic lupus erythematosus: new advances and future challenges

Lupus ◽  
2014 ◽  
Vol 23 (8) ◽  
pp. 730-742 ◽  
Author(s):  
C-G Miao ◽  
J-T Yang ◽  
Y-Y Yang ◽  
C-L Du ◽  
C Huang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Systemic Lupus ◽  
Future Challenges

scholarly journals Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study

Lupus ◽  
2021 ◽  
pp. 096120332110345
Author(s):  
Stefan Vordenbäumen ◽  
Alexander Sokolowski ◽  
Anna Rosenbaum ◽  
Claudia Gebhard ◽  
Johanna Raithel ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cd40 Ligand ◽  
Systemic Lupus ◽  
Methyl Donors ◽  
Methyl Donor ◽  
The Mean

Objective Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus

Lupus ◽  
2010 ◽  
Vol 20 (2) ◽  
pp. 131-136 ◽  
Author(s):  
CC Liu ◽  
TT Ou ◽  
CC Wu ◽  
RN Li ◽  
YC Lin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Global Dna Methylation ◽  
Systemic Lupus

DNA Methylation and Systemic Lupus Erythematosus

2007 ◽  
Vol 1108 (1) ◽  
pp. 127-136 ◽  
Author(s):  
E. BALADA ◽  
J. ORDI-ROS ◽  
M. VILARDELL-TARRES
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Systemic Lupus

Abstract 13131: Cardiovascular Manifestations and Outcomes in Systemic Lupus Erythematosus: The Cleveland Clinic Contemporary Experience

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tom Kai Ming Wang ◽  
Nicholas Chan ◽  
Mohamed Khayata ◽  
Patrick Flanagan ◽  
Richard A Grimm ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Cleveland Clinic ◽  
Cardiac Events ◽  
Systemic Lupus ◽  
Pericardial Disease ◽  
Tertiary Referral Center ◽  
Multiple Organs ◽  
Ischemic Attack ◽  
Cardiac Manifestations

Background: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting multiple organs including the heart, which when affected portends poor prognosis. Given the advances in therapies and vigilance for cardiovascular screening for SLE patients, we evaluated the contemporary cardiovascular characteristics, manifestations and outcomes in SLE patients at our tertiary referral center. Methods: Consecutive patients from the prospective SLE bio-repository at our center between October 2012 and March 2020 were included. Cardiovascular data pertaining to manifestations, investigations, management and outcomes were collected. Results: 258 SLE patients were studied, with mean age 42.2 ± 14.7 years and 233 (90.3%) females. Cardio-respiratory symptoms were present in 92 (35.7%), most commonly dyspnea in 62 (24.0%) and chest pain in 53 (20.5%). Cardiac manifestations occurred in 97 (37.6%) patients, with pericardial disease in 38 (14.7%), valvular disease in 20 (7.8%), stroke/transient ischemic attack in 20 (7.8%), coronary heart disease in 17 (6.6%) and heart failure hospitalizations in 13 (5.0%) (Table 1). During a mean follow-up of 3.0 ± 2.2 years, there were 5 (1.9%) deaths, 19 (7.4%) developed cardiac events (table 1), 6 (2.3%) had cardiovascular procedures (3 cardiac surgeries, 2 percutaneous interventions and 1 device), and 44 (17.1%) had SLE-related hospitalizations. Conclusion: Cardiac manifestations remain prevalent in SLE, especially for pericardial, valvular and atherosclerotic diseases. With appropriate contemporary SLE and cardiovascular management, subsequent medium term adverse cardiovascular outcomes are low.

scholarly journals HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Mudan Lu ◽  
Shanshan Yu ◽  
Wei Xu ◽  
Bo Gao ◽  
Sidong Xiong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Function Analysis ◽  
Critical Role ◽  
Loss Of Function ◽  
Systemic Lupus ◽  
Glycation End Products ◽  
Hmgb1 Expression

Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure.Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues.Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-αand IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response.Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

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