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首页> 美国卫生研究院文献>Antioxidants >Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis
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Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

机译：线粒体功能障碍在腹膜透析诱导的腹膜膜损伤的病理生理学中起着相关的作用

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Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.
机译：腹膜膜的保存是腹膜透析（Pd）的长期结果的基本决定因素。上皮 - 间充质转换（EMT）在PD相关腹膜损伤的发病机制中起着重要作用。我们假设线粒体可能涉及在该环境中发起和维持腹膜膜损伤的机制中。因此，我们对流出物衍生的人间皮细胞进行了前体内研究，其在保留的那些中公开了线粒体活性氧物质（MTROS）生产和线粒体细胞中的线粒体膜电位的损失。相比，与保存的那些相比，具有成纤维细胞表型。上皮形态。此外，作为EMT过程的介质作为MTOTEMPO，选择性MTROS清除剂，减少由TGF-β1诱导的纤维连接蛋白表达，鉴定MTROS作为MTROTEMPO的体外研究。此外，我们在流出物PD溶液上清液中量化了线粒体DNA（MTDNA）水平，公开了与小溶质传输特性的直接相关性（从240分钟的肌酐比透析液/血浆的比例估计），以及与腹膜超滤的反比相关。这些结果表明，线粒体参与了人类腹膜间皮细胞在PD治疗过程中遭受的EMT。 PD患者的流出物透析液中的MTDNA水平可以作为PD诱导的腹膜损伤的生物标志物。

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