Peritoneal dialysis (PD) is the most frequently applied dialysis modality in children. Unfortunately, the non-
physiological components of the dialysis fluid such as high glucose concentration and the presence of glucose-
degradation products (GDPs) and advanced glycation end products (AGEs) that are formed due to heat-sterilization
often lead to the injury of peritoneal mesothelial cells resulting in the loss of membrane integrity and thus, technical
failure of PD.
Pathological changes in the peritoneum are associated with increased stress of peritoneal mesothelial cells. Previous
research on PD has almost exclusively focused on the acute stressful effects of PD fluids where cytoprotective
heat-shock proteins (HSPs) were shown to be up-regulated in mesothelial cells to counteract toxic injury.
Unfortunately, acute PD models do not sufficiently model the clinical course of dialysis and therefore, more
sophisticated exposure models should be used. The Aufricht group has recently demonstrated that chronic exposure
of mesothelial cells to PD fluids results in blunted expression of HSPs, however the underlying signaling
mechanisms have not yet been explored. HSPs belong to the main defense mechanisms of cells against various
stress factors and therefore, they represent an attractive target of intervention to prolong and improve PD efficacy.
A particularly attractive target is represented by glycogen synthase kinase (GSK)-3ß, a protein kinase which is a
central regulator of cell stress and survival and known to be influenced by high glucose and GDPs. GSK-3ß
inactivates several target molecules among which the HSP inducing heat-shock factor-1 (HSF-1) has recently
gained more attention.
In this study, we aim to assess the role of GSK-3ß in mesothelial cells and its impact on HSF-1, HSP expression
and survival of mesothelial cells following chronic in vitro exposure to glucose based PDF with or without high
GDP content due to heat- or filter- sterilization.