Epigenetic control of autoimmune diseases: From bench to bedside

Picascia, Antonietta; Grimaldi, Vincenzo; Pignalosa, Orlando; Pascale, Maria Rosaria; Schiano, Concetta; Napoli, Claudio

doi:10.1016/j.clim.2014.12.013

Cited by 78 publications

(36 citation statements)

References 139 publications

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“…Among the histone modifications, acetylation-deacetylation represents one of the most important mechanisms of the regulation of gene expression. Histone acetyltransferase enzymes promote gene expression by transferring acetyl groups to lysine, while HDACs remove acetyl groups and are generally associated with gene repression [29]. Disruption of the histone acetylation patterns disrupts gene expression, which may manifest in disease.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

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Background: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development. Methods and Results: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6-fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001). Conclusions: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development.

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Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

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“…MiRNAs participate in various biological processes and play critical roles in the development of various diseases, including cancer, cardiovascular disease, Alzheimer’s disease, and immune system disorders [15, 16]. Abnormal miRNA expression has also been detected in patients with autoimmune diseases, such as systematic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and psoriasis [17-19]. Recently, researchers have begun to pay attention to the important roles of miRNAs in ITP, and several groups have reported that dysregulated miRNAs may be critical regulatory molecules involved in the pathogenesis of this disease.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Qian

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) have been described to have important roles in primary immune thrombocytopenia (ITP). To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. Methods: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1), chronic ITP (G2), and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. Results: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed) and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. Conclusion: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

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“…Segundo Picascia et al, (2015), os miRNAs possuem uma função dinâmica na regulação da imunidade inata e adaptativa, salientando assim a sua função no processo da autoimunidade.…”

Section: Fonte: (Zhou Et Al 2014)unclassified

Processo epigenéticos envolvidos na fisiopatologia da esclerose múltipla com ênfase na função dos miRNAs

Siqueira

Pires

2017

Semin. Cienc. Biol. Saude

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Abstract1 Biomédica formada pela Universidade Tuiuti do Paraná. E-mail: mks.siqueira@gmail.com 2 Mestre em Ciências (Bioquímica) pela Universidade Federal do Paraná. Professora da Universidade Tuiuti do Paraná. E-mail:liliane.acupuntura@gmail.com DOI: 10.5433/1679 Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system (CNS). The pathophysiology is characterized by intense inflammatory activity and involvement of immune cells (CD4 +, CD8 + and B cells); glial cells and disrupted permeability of the blood brain barrier (BBB). Currently, its etiology remains unknown; it is believed that environmental factors and genetic predisposition are responsible for the autoimmunity. Discrepancies in genetic inheritance patterns of disease, prevalence of gender and low concordance rate between homozygous twins suggest participation of epigenetic processes in multiple sclerosis. Epigenetic processes are responsible for gene expression without causing changes in the genetic code and are highly sensitive to environmental variations. In addition, they are preserved between cell division and interfere in different biological processes; however, they can be reversed. The three most studied processes are DNA methylation, histone acetylation and gene silencing by miRNAs. miRNAs are specifically being studied since they regulate one third of gene expression in mammals. These small RNA segments of approximately 22 nucleotides have elucidated several aspects of MS and seem to interact and regulate immune system and CNS; they may become valuable biomarkers for that disease.A esclerose múltipla (EM) é uma doença neurodegenerativa autoimune do sistema nervoso central (SNC). A fisiopatologia caracteriza-se por intensa atividade inflamatória e envolvimento de células do sistema imune (TCD4+, TCD8+ e linfócitos B); células da glia e uma desregulação da permeabilidade da barreira hematoencefálica (BHE). Atualmente a sua etiologia permanece desconhecida e acreditase que os fatores ambientais e uma predisposição genética sejam os responsáveis pela autoimunidade. Discrepâncias em padrões de herança genética da doença, prevalência de gênero e baixa taxa de concordância entre gêmeos homozigotos sugerem a atuação de processos epigenéticos na esclerose múltipla. Os processos epigenéticos são responsáveis pela expressão gênica sem ocasionar uma alteração no código genético e são altamente sensíveis a variações do meio ambiente. Ademais são preservados entre divisões celulares e interferem em diferentes processos biológicos; porém podem ser revertidos. Os três processos mais bem estudados são a metilação de DNA, a acetilação de histonas e o silenciamento gênico por miRNAs. Os miRNAs especificamente vem sendo alvo de pesquisas uma vez que regulam um terço da expressão gênica em mamíferos. Esses pequenos segmentos de RNA de aproximadamente 22 nucleotídeos têm elucidado diversos aspectos da EM e parecem interagir e regular células do sistema imune e do SNC; podendo vir a se tornar valiosos biomarcadores para a mesma...

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Epigenetic control of autoimmune diseases: From bench to bedside

Cited by 78 publications

References 139 publications

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

Processo epigenéticos envolvidos na fisiopatologia da esclerose múltipla com ênfase na função dos miRNAs

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