Roel Bijkerk
Post-transcriptional regulation of kidney pathophysiology
Chronic kidney disease (CKD) affects one in every ten adults in the Netherlands, with a worldwide prevalence of about 8%. Besides its high morbidity, CKD is a leading cause of death due to premature cardiovascular disease. With the ageing population and the increasing prevalence of non-communicable diseases such as diabetes and hypertension, the numbers of CKD patients are ever increasing.
The ongoing decline in kidney function in CKD patients ultimately leads to a complete dependence on renal replacement therapy. Although kidney transplantation can provide a significant improvement in the quality of life compared to dialysis protocols (the 5-year survival rate of patients on dialysis is only 35%), the limited number of suitable donors and the complications of immunosuppressive therapy continues to drive the quest for alternative therapeutic approaches.
Recently, evidence is accumulating that kidney regeneration and cellular responses to injury are largely regulated at the post-transcriptional level involving an intricate interplay between non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and RNA-binding proteins. MiRNAs are currently the most widely-studied class of non-coding RNAs that destabilize RNA and/or inhibit protein translation, and can simultaneously repress multiple genes to directly influence the output of functionally-related biological pathways. Also lncRNAs, which have specific, regulated patterns of expression in cell types and tissues, have gained interest as novel regulators of gene expression. Both MiRNAs and lncRNAs control cell fate via temporal and spatial gene regulation and have been demonstrated to be essential in phenotypic cellular reprogramming events such as those involved in the re- and de-differentiation of progenitor cells. As such, elucidating post-transcriptional networks that drive kidney injury and repair processes may provide us with potentially modifiable therapeutic targets to counteract the development of CKD.
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Research
- Circulating noncoding RNA as posttranscriptional determinant of cardiovascular complications in CKD
- Long noncoding RNAs as a determinant of microvascular stability in chronic kidney disease
- Post-transcriptional regulation as a key driver of intrinsic kidney regeneration
- Vascular Nephrology Group Research