Fluid flow stress affects peritoneal cell kinetics: possible pathogenesis of peritoneal fibrosis
| Autor: | Shuji Toda, Hajime Sugihara, Shigehisa Aoki, Namie Nomoto, Akinori Nagashima, Toshiaki Takezawa, Aki Matsunobu, Kazuyoshi Uchihashi, Junichi Makino, Toru Sanai |
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| Rok vydání: | 2011 |
| Předmět: |
Cell kinetics
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition medicine.medical_treatment Peritoneal dialysis Pathogenesis Fibrosis Dialysis Solutions Medicine Humans Epithelial–mesenchymal transition Peritoneal Fibrosis Cells Cultured Hyperplasia business.industry Epithelial Cells General Medicine medicine.disease Nephrology Stress Mechanical Mitogen-Activated Protein Kinases Peritoneum business Complication Rheology Peritoneal Dialysis |
| Zdroj: | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 31(4) |
| ISSN: | 1718-4304 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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