Altered DNA methylation in kidney disease: useful markers and therapeutic targets

Recent studies have demonstrated the association of altered epigenomes with lifestyle-related diseases. Epigenetic regulation promotes biological plasticity in response to environmental changes, and such plasticity may cause a 'memory effect', a sustained effect of transient treatment or an insult in the course of lifestyle-related diseases. We investigated the significance of epigenetic changes in several genes required for renal integrity, including the nephrin gene in podocytes, and the sustained anti-proteinuric effect, focusing on the transcription factor Krüppel-like factor 4 (KLF4). We further reported the role of the DNA repair factor lysine-acetyl transferase 5 (KAT5), which acts coordinately with KLF4, in podocyte injury caused by a hyperglycemic state through the acceleration of DNA damage and epigenetic alteration. In contrast, KAT5 in proximal tubular cells prevents acute kidney injury via glomerular filtration regulation by an epigenetic mechanism as well as promotion of DNA repair, indicating the cell type-specific action and roles of DNA repair factors. This review summarizes epigenetic alterations in kidney diseases, especially DNA methylation, and their utility as markers and potential therapeutic targets. Focusing on transcription factors or DNA damage repair factors associated with epigenetic changes may be meaningful due to their cell-specific expression or action. We believe that a better understanding of epigenetic alterations in the kidney will lead to the development of a novel strategy for chronic kidney disease (CKD) treatment.