title: Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease.
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 methylatedRASAL1promoter DNA fragments in peripheral blood correspond with levels of intrarenal levels ofRASAL1promoter methylation and degree of fibrosis in kidney biopsies, enabling non-invasive longitudinal analysis of intrarenal CpG island methylation.
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany ; Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA.
authors.forename: Björn
authors.initials: B
authors.lastname: Tampe
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany ; Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA.
authors.forename: Desiree
authors.initials: D
authors.lastname: Tampe
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA ; Department of Cardiology and Pneumology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany ; German Center for Cardiovascular Research (DZHK), Robert Koch Street 40, Göttingen, Germany.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Zeisberg
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA ; Renal Division, University Hospital Freiburg, Hugstetter Street 55, Freiburg, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Bechtel-Walz
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA ; Department of Cancer Biology and the Metastasis Research Center, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, USA.
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
authors.affiliation: Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Robert Koch Street 40, Göttingen, Germany ; Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeisberg
keywords: DNA methylation; De-methylation; Epigenetics; Fibrosis; RASAL1; Ten-Eleven Translocation (TET)