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首页> 外文期刊>Apoptosis >Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis
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Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis

机译：基质金属蛋白酶和可溶性Fas / FasL系统作为慢性透析的儿童和年轻人的凋亡新调节剂

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The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA. Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations. Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms.
机译：膜受体Fas及其配体FasL的系统构成触发凋亡的主要途径之一。但是，它们的可溶形式的作用尚未阐明。尽管sFasL可以通过基质金属蛋白酶（MMP）从膜结合形式转化，但尚无关于慢性透析患者（无论儿童还是成人）中sFas / sFasL，MMP及其组织抑制剂（TIMP）之间关系的数据。我们研究的目的是评估慢性透析儿童和年轻人中sFas，sFasL及其潜在调节剂（MMP-2，MMP-7，MMP-9，TIMP-1，TIMP-2）的血清浓度。检查了22例接受自动腹膜透析（APD）的儿童，19例接受血液透析（HD）的患者和30例对照。通过ELISA评估血清sFas，sFasL，MMP和TIMP的浓度。与对照组相比，所有透析患者的sFas，sFasL，sFas / sFasL比值，MMP-2，MMP-7，MMP-9，TIMP-1和TIMP-2的中位数值均显着升高，在高清一次高清会议导致所有参数值降低到低于APD儿童的水平。回归分析表明，MMP-7和TIMP-1是sFas和sFasL浓度的最佳预测指标。进行慢性透析的儿童和年轻人容易出现sFas / sFasL系统功能异常，在进行血液透析的患者中更为明显。 sFas / sFasL与检测的酶之间的相关性表明，MMP和TIMP参与慢性透析对小儿群体细胞死亡的调节，从而触发了抗（sFas）和促凋亡（sFasL）机制。

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