Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease.

Tampe, Björn; Tampe, Desiree; Zeisberg, Elisabeth M; Müller, Gerhard A; Bechtel-Walz, Wibke; Koziolek, Michael; Kalluri, Raghu; Zeisberg, Michael · EBioMedicine · 2015

basic_science · Level V

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Abstract

Progression of chronic kidney disease remains a principal problem in clinical nephrology and there is a pressing need for novel therapeutics and biomarkers. Aberrant promoter CpG island methylation and subsequent transcriptional silencing of specific genes have emerged as contributors to progression of chronic kidney disease. Here, we report that transcriptional silencing of the Ras-GTP suppressor RASAL1 contributes causally to progression of kidney fibrosis and we identified that circulating methylated <i>RASAL1</i> promoter DNA fragments in peripheral blood correspond with levels of intrarenal levels of <i>RASAL1</i> promoter methylation and degree of fibrosis in kidney biopsies, enabling non-invasive longitudinal analysis of intrarenal CpG island methylation.