Abstract
Enhanced apoptosis is characteristic for chronic kidney disease (CKD). A specific type of apoptosis, anoikis, is connected with the extracellular matrix turnover and cell detachment. Although E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD. The aim of study was to evaluate the serum concentrations of E-cadherin, EMMPRIN and their potential regulators (MMP-8, MMP-7, TIMP-1, TIMP-2), with relevance to apoptosis/cell damage markers (sFas, sFasL, Hsp27), in children with CKD. 39 CKD children stages 3–4, 26 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 those parameters were assessed by ELISA. Median E-cadherin, EMMPRIN and MMP-8 values were significantly increased in patients on dialysis versus those in pre-dialysis period and versus controls. The highest values were noticed in the HD subjects. Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients. Children with CKD are prone to E-cadherin, EMMPRIN and MMP-8 elevation, aggravated by the dialysis commencement and most evident on hemodialysis. Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis. E-cadherin seems the most accurate marker of anoikis in this population.
Highlights
Enhanced apoptosis is one of the features characteristic for chronic kidney disease (CKD), aggravating with the dialysis commencement and the use of bioincompatible membranes [1, 2]
E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD
Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients
Summary
Enhanced apoptosis is one of the features characteristic for chronic kidney disease (CKD), aggravating with the dialysis commencement and the use of bioincompatible membranes [1, 2]. Anoikis is a specific form of apoptosis, affecting cells that have lost their anchorage in the original milieu [3]. It protects them against migration, reattachment in inappropriate location and metastatic spread. E-cadherin is an adhesion molecule responsible for interactions between neighbouring cells. It has been shown that E-cadherin cleavage may be a caspase-dependent apoptotic process, where the loss of staining on the cell surface is followed by the accumulation of adhesion molecule in the cytosol [7]. E-cadherin can be a proteolytic target for MMP-7, cleaving an ectodomain with invasive paracrine features [8]. Like other metalloproteinases, MMP-7 eases cancer invasion by proteolysis of extracellular matrix components and cell detachment
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