FLUID FLOW STRESS AFFECTS PERITONEAL CELL KINETICS: POSSIBLE PATHOGENESIS OF PERITONEAL FIBROSIS
FLUID FLOW STRESS AFFECTS PERITONEAL CELL KINETICS: POSSIBLE PATHOGENESIS OF PERITONEAL FIBROSIS
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DOI：
10.3747/pdi.2010.00157
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发表时间：
2011-07-01
影响因子：
2.8
通讯作者：
Toda, Shuji
中科院分区：
文献类型：
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作者：
Aoki, Shigehisa;Makino, Junichi;Toda, Shuji
背景：腹膜纤维化是包裹性腹膜硬化症（EPS）发展的一个重要的先兆条件。这种严重的并发症导致腹膜透析（PD）患者的高死亡率。尽管有几个因素，包括透析液中的高浓度葡萄糖，被认为是腹膜纤维化的有效因子，但其潜在机制仍不清楚。在腹膜透析过程中，透析液在透析和身体运动的作用下持续对腹膜产生流体流动应力。流体流动应力已被认为在许多细胞类型的生理反应中起关键作用。因此，我们假设，流体流动应力可能参与腹膜纤维化的发病机制，导致EPS.Methods：要产生流体流动应力，培养容器放置在一个旋转振荡器在一个旋转室。在该系统中，振荡器以25 rpm的速度旋转，半径为1.5 cm。结果：流动应力可促进间皮细胞的增殖和上皮-间质转化（EMT），且与葡萄糖浓度无关。流体流动应激抑制间皮细胞ERK（细胞外信号调节激酶）和p38 MAPK（丝裂原活化蛋白激酶）的表达。ERK和p38 MAPK抑制剂的管理复制的应力诱导的mesothelialcells.Conclusions形态：目前的数据表明，流体流动应力促进增生和EMT的mesothelialcells通过MAPK轴，表明流体流动应力可能参与腹膜纤维化的发病机制。
Background: Peritoneal fibrosis is an essential precursor condition to the development of encapsulating peritoneal sclerosis (EPS). This serious complication leads to a high mortality rate in peritoneal dialysis (PD) patients. Although several factors, including highly concentrated glucose in the dialysis solution, are believed to be potent agents for peritoneal fibrosis, the underlying mechanism remains unclear. During PD, the dialysis solution continuously generates fluid flow stress to the peritoneum under peristalsis and body motion. Fluid flow stress has been implicated as playing a critical role in the physiologic responses of many cell types. We therefore hypothesized that fluid flow stress may be involved in the pathogenesis of peritoneal fibrosis leading to EPS.Methods: To generate fluid flow stress, culture containers were placed on a rotatory shaker in a thermostatic chamber. In this system, the shaker rotated at a speed of 25 rpm with a radius of 1.5 cm. Mesothelial cells were cultured in low-glucose (1000 mg/L) or high-glucose (4500 mg/L) complete medium with and without flow stress.Results: Fluid flow stress promoted hyperplasia and epithelial-mesenchymal transition (EMT) of mesothelial cells independent of glucose concentration. Fluid flow stress inhibited expression of ERK (extracellular signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) in mesothelial cells. Administration of ERK and p38 MAPK inhibitors replicated the stress-induced morphology of mesothelial cells.Conclusions: The present data indicate that fluid flow stress promotes hyperplasia and EMT of mesothelial cells via the MAPK axis, suggesting that fluid flow stress may be involved in the pathogenesis of peritoneal fibrosis.