Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis

Neary, Roisín; Watson, Chris; Baugh, John

doi:10.1186/s13069-015-0035-8

Cited by 63 publications

(46 citation statements)

References 105 publications

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“…Genome-wide methylation studies on fibroblasts from idiopathic pulmonary fibrosis and nonfibrotic controls showed significant differences in DNA methylation (124-126). Similarly, changes in DNA methylation are associated with systemic sclerosis and with fibrosis in wound healing (127, 128). A methylation study of 18 candidate genes found a marginally significant association (P<0.05) between hypermethylation in the promoter region of the XRCC2 gene and late toxicity in cervical cancer patients treated with chemoradiotherapy (129).…”

Section: ‘Omics’ Approachesmentioning

confidence: 99%

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

et al. 2016

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Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy.

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Section: ‘Omics’ Approachesmentioning

confidence: 99%

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

et al. 2016

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“…DNAm studies in chronic kidney disease (CKD) show the role of methylation in abnormal wound healing process that results in fibrogenesis (16,27–29). In transplantation, only a few studies were done addressing DNAm changes (25,27,29–31).…”

Section: Introductionmentioning

confidence: 99%

“…In transplantation, only a few studies were done addressing DNAm changes (25,27,29–31). However, these studies mostly used reductionist systems limited to one or few gene sets and were limited to mouse and cell-based models.…”

Section: Introductionmentioning

confidence: 99%

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Bontha

Maluf

Archer

et al. 2017

American Journal of Transplantation

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Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and non-immunological insults lead to interstitial fibrosis and tubular atrophy (IFTA) and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected after 24-months post transplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2-years post-transplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.

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“…Progression of chronic kidney disease is associated with substantial and consistent changes of renal methylation patters, providing correlative evidence for contribution to disease progression [28,29]. First causal evidence for a role of aberrant DNA methylation in kidney fibrosis stems from studies, in which fibrosis in mouse models of renal fibrosis were ameliorated by treatment with the de-methylating drug 5' Azacytidine (5' Aza) [19].…”

Section: Contribution Of Aberrant Dna Methylation To Fibroblast Activmentioning

confidence: 99%

Inhibition of Fibrogenesis upon Hydralazine-induced DNA Demethylation

Em¹,

Zeisberg²

2015

J Kidney

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Chronic progressive kidney disease (CKD) remains an unsolved problem in clinical Nephrology as neither biomarkers to predict progression towards end-stage renal failure in individual patients nor specific drugs to inhibit decline of kidney function are available in the clinic yet. In this regard, the prototypical epigenetic mechanism of CpG island promoter methylation has emerged as modulator of disease progression with utilities both as biomarker and as therapeutic target. Recent studies demonstrated the potential of hydralazine, a long-established antihypertensive drug with de-methylating activity, to reverse aberrant CpG island promoter aberration and ameliorate progression of chronic kidney disease. Here we review contribution of aberrant promoter methylation to progression of fibrogenesis and mechanisms underlying hydralazine's demethylating activity and discuss possible translational implications.Citation: Zeisberg EM, Zeisberg M (2016) Inhibition of Fibrogenesis upon Hydralazine-induced DNA Demethylation. J Kidney 2: 124.

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Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis

Cited by 63 publications

References 105 publications

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Inhibition of Fibrogenesis upon Hydralazine-induced DNA Demethylation

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