Chronic kidney disease encompasses all renal conditions which, irrespective of their cause, are characterized by histomorphological damage and/or a decreased glomerular filtration rate (<60 ml/min/1,73m2), either of which are present for at least 3 months. Up to now, end stage renal disease (i.e. the final stage of chronic kidney disease) can only be treated by dialysis or transplantation.
DNA methylation is an epigenetic modification of DNA governed by DNA methyltransferases (Dnmts). DNA methylation generally suppresses transcription and plays an important role in the development of cancer. It also is an important etiological factor in other pathologies, such as renal fibrosis. Fibrosis is the cell biological process underlying chronic kidney disease. By losing control of the normal reparing fibrotic process, healthy tissue is affected and progressively replaced by non-functional fibrous tissue. Two renal cell types play a crucial role herein: (1) the proximal tubular epithelial cell, which produces pro-fibrotic cytokines (TGF-β, CTGF) in response to damage/stress, and (2) the fibroblast, which in a pro-fibrotic environment is activated to proliferate and produce extracellular matrix (ECM, fibrous deposition). If exposure of fibroblasts to this environment is sufficiently long, fibroblasts get terminally activated, resulting in chronic renal fibrosis. Up to now, the role of DNA methylation in the PTC is unknown.
The goals of this project are: 1) identification of differentially methylated genes of PTCs associated with development of chronic kidney disease after acute kidney injury and 2) correlating DNA methylome and RNA-transcriptome analysis in PTC, urine and blood in order to progress towards diagnostic and therapeutic markers.