Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

Wuttge, Dirk M.; Carlsen, Anting Liu; Teku, Gabriel; Steen, Samantha O.; Wildt, Marie; Vihinen, Mauno; Hesselstrand, Roger; Heegaard, Niels H. H.

doi:10.1093/rheumatology/kev234

Cited by 31 publications

(19 citation statements)

References 18 publications

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“…The miR-92a family regulates fundamental processes in the development of mammalian organs including heart, blood vessel formation, lungs and the immune system. Among these, miR-92a-3p acquires specific relevance lacking for other miRNAs, because decreased circulating levels have been associated with interstitial lung disease (ILD) in SSc patients [21]. However, this association was not confirmed in another study.…”

Section: Mir-92a-3p In Ipf and Ssc Fibrogenesismentioning

confidence: 92%

“…For example, miR-210, miR-17-5p, miR-155-5p and miR-101-3p show contradictory results [21,29,30,37,42,46,48,49]. Of note, opposite results have been described for miR-125a-5p and 133b-3p: both are downregulated in SSc tissues [24,37] and upregulated in IPF lungs [40,42].…”

Section: Minor Overlapping Mirnasmentioning

confidence: 96%

“…Evidence suggests that miR-92a downregulates MMP-1 expression, which is an enzyme that degrades the ECM [21,24,[34][35][36]. Increased levels can therefore lead to reduced collagen degradation.…”

Section: Mir-92a-3p In Ipf and Ssc Fibrogenesismentioning

confidence: 99%

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A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

Bagnato¹,

Roberts²,

Roman³

et al. 2017

Eur Respir Rev

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Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential.

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Section: Mir-92a-3p In Ipf and Ssc Fibrogenesismentioning

confidence: 92%

Section: Minor Overlapping Mirnasmentioning

confidence: 96%

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A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

Bagnato¹,

Roberts²,

Roman³

et al. 2017

Eur Respir Rev

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“…Koba et al observed different miRNA expression patterns in SSc compared to healthy controls, and that combining miR-206 and miR-21 may be more informative in distinguishing SSc patients from healthy subjects than either miRNA alone [152]. Wuttge et al examined circulating miRNA expression profiles and their correlation with disease phenotype and autoantibody status [153]. They identified 4 miRNAs (miR-223, -181b, -342-3p, -184) that were differentially expressed between diffuse SSc and limited SSc, and that 5 miRNAs (miR-409-3p, -184, -92a, -29a, -101) were differentially expressed in one or more autoantibody groups; both of which further confirmed by logistic regression and receiver operating characteristic curve analysis.…”

Section: Epigenetic Impact In Ssc Pathogenesismentioning

confidence: 99%

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

Tsou

Sawalha

2017

Journal of Autoimmunity

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With unknown etiology, scleroderma (SSc) is a multifaceted disease that comprises of immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated miRNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that were affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomincs and epigenomics research in SSc.

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“…MiRNA‐223, ‐181b, ‐342‐3p and ‐184 were differentially expressed in the lSSc and dSSc groups, and miRNA‐409, ‐184, ‐92a, ‐29a and ‐101 exhibited greatly different levels in one or more autoantibody groups. Specific miRNAs were associated with autoantibody profiles of known diagnostic and prognostic value . A 21‐miRNA combined model was constructed with optimum accuracy (80%) to differentiate SSc from both normal subjects and those with lupus.…”

Section: Global Epigenetics and Sscmentioning

confidence: 99%

Systematic approach to understanding the pathogenesis of systemic sclerosis

et al. 2017

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Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers.

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Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

Cited by 31 publications

References 18 publications

A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

Systematic approach to understanding the pathogenesis of systemic sclerosis

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