Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
Biochem Biophys Res Commun. 2011 Dec 16;416(3-4):391-6. doi: 10.1016/j.bbrc.2011.11.051. Epub 2011 Nov 19.
Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination of fluid streaming. These findings support the hypothesis that a history of PD for a certain period could serve as a trigger of EPS after stoppage of PD.
包裹性腹膜硬化症（EPS）通常在转为血液透析和移植后发展。腹膜透析（PD）终止和与移植相关的因素都是 PD 后发生 EPS 的风险因素，但这种迟发性腹膜纤维化的确切机制仍有待阐明。我们之前的研究表明，流体流动应激通过丝裂原活化蛋白激酶（MAPK）信号诱导间皮细胞增殖和上皮-间充质转化。因此，我们推测，流体流动应激的长期生物活性效应可能会影响停止流体流动后的间皮细胞动力学。为了研究在停止流体流动后，间皮细胞在流体流动应激的生物活性效应下能持续多长时间，我们首先在流体流动应激下培养间皮细胞，然后在静态条件下培养细胞。与静止条件相比，暴露于一定时间的流体流动应激的间皮细胞在停止流体流动后表现出明显更高的增殖活性。蛋白磷酸酶 2A（PP2A）的表达水平随时间而变化，与暴露于流体流动应激的时间有关，呈双相模式。一旦经过一定的时间，间皮细胞对流体流动应激的生物活性效应就没有差异。这些发现表明，在停止流体流动后，流体流动应激对间皮细胞产生持久的生物活性效应。这些发现支持了这样一种假设，即一定时间的 PD 病史可能是 PD 停止后 EPS 的触发因素。
