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Targeting DNA Methylation in Podocytes to Overcome Chronic Kidney Disease.
Keio Journal of Medicine 2023 June 4
The number of patients with chronic kidney disease (CKD) is on the rise worldwide, and there is urgent need for the development of effective plans against the increasing incidence of CKD. Podocytes, glomerular epithelial cells, are an integral part of the primary filtration unit of the kidney and form a slit membrane as a barrier to prevent proteinuria. The role of podocytes in the pathogenesis and progression of CKD is now recognized. Podocyte function depends on a specialized morphology with the arranged foot processes, which is directly related to their function. Epigenetic changes responsible for the regulation of gene expression related to podocyte morphology have been shown to be important in the pathogenesis of CKD. Although epigenetic mechanisms include DNA methylation, histone modifications, and RNA-based regulation, we have focused on DNA methylation changes because they are more stable than other epigenetic modifications. This review summarizes recent literature about the role of altered DNA methylation in the kidney, especially in glomerular podocytes, focusing on transcription factors and DNA damage responses that are closely associated with the formation of DNA methylation changes.
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