Epigenetics are defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, and include higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. This dynamic epigenetic layer responds to external environmental signals to influence the expression of genes associated with disease states. Recently, much consideration has been focused to the role and the function of epigenetics in the cellular and subcellular pathways and in the regulation of genes in the setting of kidney disease.
The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other environmental stimuli can yield novel insights into the pathogenesis of kidney diseases.
Further evaluation of the effect of epigenetic modifications occurring in ischemia reperfusion injury, progression to kidney fibrosis (in native and transplanted kidneys), diabetic nephropathy, hypertension and kidney disease, among others will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the disease kidney.
Major epigenetic modifications influence inflammatory and pro-fibrotic genes to perpetuate renal disease progression. Epigenetic modifications may add to improving our ability to explain the heterogeneity of kidney disease progression rates of individual patients. Basic scientific animal models, clinical studies and the diagnostic potential to produce large amounts of epigenomic data suggest a critical role for epigenetic modifications in renal development and kidney disease progression.
More than ever, an urgent need exists for the discovery of new diagnostics, biomarkers and therapies in clinical nephrology to tackle the central problem of the near unstoppable progression of renal diseases. Likewise, there is a great need to identify biological markers that help to recognize patients who are at a higher risk of developing chronic kidney disease (CKD) than others, so that targeted therapies can be used to delay the onset or progression of CKD. Recent advances and decrease in costs of next-generation sequencing can improve the understanding of epigenetic risk factors and lead to the identification of a clinically useful epigenetic risk profile using kidney samples.
However, the cellular heterogeneity of the kidney and the invasive nature of kidney biopsies might limit the usefulness of this technique to mechanistic evaluations but not for routine clinical use. Body fluids can be minimally invasive samples and thus represent easily accessible reservoirs for epigenetic biomarkers. Their ready accessibility in blood and urine makes miRNAs attractive biomarkers or targets for therapeutic intervention. Moreover, as epigenetics modifications are dynamic and reversible, they represent potential therapeutic interventions based on improved specificity on strategies to be used.
This Research Topic will highlight recent basic, pre-clinical and clinical progress and opportunities related to further understanding of epigenetic modifications (i.e., DNA methylation, noncoding RNAs) on downstream pathways inducing kidney disease, their utility for better stratification of disease risk and prognosis, and evaluation of strategies to target specific epigenetic modifications that may avoid or decrease renal injury pathways using drugs and biologic agents by publishing relevant full length and short original research communications as well as opinion and review articles.
Epigenetics are defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, and include higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. This dynamic epigenetic layer responds to external environmental signals to influence the expression of genes associated with disease states. Recently, much consideration has been focused to the role and the function of epigenetics in the cellular and subcellular pathways and in the regulation of genes in the setting of kidney disease.
The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other environmental stimuli can yield novel insights into the pathogenesis of kidney diseases.
Further evaluation of the effect of epigenetic modifications occurring in ischemia reperfusion injury, progression to kidney fibrosis (in native and transplanted kidneys), diabetic nephropathy, hypertension and kidney disease, among others will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the disease kidney.
Major epigenetic modifications influence inflammatory and pro-fibrotic genes to perpetuate renal disease progression. Epigenetic modifications may add to improving our ability to explain the heterogeneity of kidney disease progression rates of individual patients. Basic scientific animal models, clinical studies and the diagnostic potential to produce large amounts of epigenomic data suggest a critical role for epigenetic modifications in renal development and kidney disease progression.
More than ever, an urgent need exists for the discovery of new diagnostics, biomarkers and therapies in clinical nephrology to tackle the central problem of the near unstoppable progression of renal diseases. Likewise, there is a great need to identify biological markers that help to recognize patients who are at a higher risk of developing chronic kidney disease (CKD) than others, so that targeted therapies can be used to delay the onset or progression of CKD. Recent advances and decrease in costs of next-generation sequencing can improve the understanding of epigenetic risk factors and lead to the identification of a clinically useful epigenetic risk profile using kidney samples.
However, the cellular heterogeneity of the kidney and the invasive nature of kidney biopsies might limit the usefulness of this technique to mechanistic evaluations but not for routine clinical use. Body fluids can be minimally invasive samples and thus represent easily accessible reservoirs for epigenetic biomarkers. Their ready accessibility in blood and urine makes miRNAs attractive biomarkers or targets for therapeutic intervention. Moreover, as epigenetics modifications are dynamic and reversible, they represent potential therapeutic interventions based on improved specificity on strategies to be used.
This Research Topic will highlight recent basic, pre-clinical and clinical progress and opportunities related to further understanding of epigenetic modifications (i.e., DNA methylation, noncoding RNAs) on downstream pathways inducing kidney disease, their utility for better stratification of disease risk and prognosis, and evaluation of strategies to target specific epigenetic modifications that may avoid or decrease renal injury pathways using drugs and biologic agents by publishing relevant full length and short original research communications as well as opinion and review articles.
