Abstract
Intracellular heat shock protein (Hsp) 27 is a potent anti-apoptotic factor that, among other activities, prevents the binding of membrane receptor Fas to its ligand FasL. However, the potential role of extracellular Hsp27 and possibilities to control it have not been clarified. Moreover, there are no data on relations between Hsp27, sFas/sFasL system, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in patients with chronic kidney disease (CKD)—neither children nor adults. The aim of this study was to evaluate serum concentrations of Hsp27 and their potential regulators (sFas, sFasL, MMP-7, TIMP-1) in children with CKD and on chronic dialysis. Twenty-six CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD), and 30 controls were examined. Serum concentrations of Hsp27, sFas, sFasL, MMP-7, and TIMP-1 were assessed by ELISA. Median values of Hsp27 were significantly elevated in all dialyzed patients vs. those in pre-dialysis period and vs. controls, the highest values being observed in subjects on HD. Regression analysis revealed that MMP-7, TIMP-1, sFas, and sFasL were the best predictors of Hsp27 concentrations in dialyzed patients. Children with CKD are prone to Hsp27 dysfunction, aggravated by the dialysis commencement, and more pronounced in patients on hemodialysis. Correlations between Hsp27 and examined parameters suggest the potential role for Hsp27 as a marker of cell damage in the pediatric population on chronic dialysis.
Highlights
Chronic inflammation, immune system activation, and enhanced apoptosis are characteristic features of chronic kidney disease (CKD), aggravated by the dialysis procedure and the membrane type (Andreoli et al 2007; Soriano et al 2005)
We investigated the correlations between Hsp27, matrix metalloproteinases (MMP-7), their tissue inhibitors (TIMP-1), markers of inflammation, and endothelial damage in the pediatric population with CKD
Our study describes for the first time the disturbed Hsp27 concentrations, and the potential role of sFas/sFasL, MMP-7 and TIMP-1 in their regulation, in children with chronic kidney disease treated conservatively and on chronic dialysis
Summary
Immune system activation, and enhanced apoptosis are characteristic features of chronic kidney disease (CKD), aggravated by the dialysis procedure and the membrane type (Andreoli et al 2007; Soriano et al 2005). Intracellular Hsp seems to play a crucial role in apoptosis regulation, controlling both intrinsic and extrinsic pathways of programmed cell death (Concannon et al 2003; SanchezNino et al 2012). The extrinsic one is initiated by the binding of membrane receptor Fas to its ligand FasL. This action can be inhibited by Hsp, blocking the Daxx translocation to the membrane and its interaction with Fas (Nagata and Goldstein 1995; Charette et al 2000). Hsp can regulate negatively apoptosis by both upstream and downstream inhibition of cytochrome c release (Concannon et al 2003). There are no data on the character of Hsp27/Fas/FasL intracellular interactions in the course of chronic kidney disease or under dialysis conditions
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