Distinct patterns of transcriptional and epigenetic alterations characterize acute and chronic kidney injury
Open Access
- 14 December 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 8 (1), 1-15
- https://doi.org/10.1038/s41598-018-35943-x
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered early and late phases of a pathologic continuum of interconnected disease states. Although changes in gene expression patterns have recently been elucidated for the transition of AKI to CKD, the epigenetic regulation of key kidney injury related genes remains poorly understood. We used multiplex RT-qPCR, ChIP-qPCR and integrative analysis to compare transcriptional and epigenetic changes at renal disease-associated genes across mouse AKI and CKD models. These studies showed that: (i) there are subsets of genes with distinct transcriptional and epigenetically profiles shared by AKI and CKD but also subsets that are specific to either the early or late stages of renal injury; (ii) differences in expression of a small number of genes is sufficient to distinguish AKI from CKD; (iii) transcription plays a key role in the upregulation of both AKI and CKD genes while post-transcriptional regulation appears to play a more significant role in decreased expression of both AKI and CKD genes; and (iv) subsets of transcriptionally upregulated genes share epigenetic similarities while downregulated genes do not. Collectively, our study suggests that identified common transcriptional and epigenetic profiles of kidney injury loci could be exploited for therapeutic targeting in AKI and CKD.Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (DK073497, DK083648, DK38432, DK094934, GM111439, CA191135)
This publication has 95 references indexed in Scilit:
- In vivo regulation of the heme oxygenase-1 gene in humanized transgenic miceKidney International, 2012
- Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and “end-stage” kidney diseaseAmerican Journal of Physiology-Renal Physiology, 2011
- Repair of injured proximal tubule does not involve specialized progenitorsProceedings of the National Academy of Sciences of the United States of America, 2011
- Regulation of chromatin by histone modificationsCell Research, 2011
- The role of spermidine/spermine N1-acetyltransferase in endotoxin-induced acute kidney injuryAmerican Journal of Physiology-Cell Physiology, 2010
- Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surfaceCellular Signalling, 2010
- The cell cycle and acute kidney injuryKidney International, 2009
- Renal ischemia-reperfusion injury upregulates histone-modifying enzyme systems and alters histone expression at proinflammatory/profibrotic genesAmerican Journal of Physiology-Renal Physiology, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Microplate-based chromatin immunoprecipitation method, Matrix ChIP: a platform to study signaling of complex genomic eventsNucleic Acids Research, 2008