Integration of DNA Methylome and Transcriptome Analysis to Identify Novel Epigenetic Targets in the Acute Kidney Injury–Chronic Kidney Disease Transition

Abstract

(1) Background: the epigenetic mechanisms underlying the progression from acute kidney injury (AKI) to chronic kidney disease (CKD) remain poorly understood; (2) Methods: to investigate this process, we conducted genome-wide DNA methylation sequencing to map the epigenetic changes during the AKI-CKD transition in a mouse model. By integrating DNA methylome and transcriptome analyses, we identified genes and signaling pathways regulated by DNA methylation throughout this progression; (3) Results: our analysis identified four candidate genes—Atp1a3, Ncf1, Lpl, and Slc27a2—that were regulated by DNA methylation and strongly correlated with kidney disease prognosis. Additionally, we found that the PPAR signaling pathways, among others, were implicated in this process. Treatment with DNA methyltransferase inhibitors mitigated fibrosis and improved lipid metabolism in the kidneys during AKI-CKD progression; (4) Conclusions: this study provides the first comprehensive epigenetic map of the AKI-CKD transition. Our findings offer new insights into the epigenetic regulation of kidney disease progression and highlight potential therapeutic targets to prevent the transition from AKI to CKD.