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Fluid flow stress affects peritoneal cell kinetics: possible pathogenesis of peritoneal fibrosis.

AbstractBACKGROUND:
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.
AuthorsShigehisa Aoki, Junichi Makino, Akinori Nagashima, Toshiaki Takezawa, Namie Nomoto, Kazuyoshi Uchihashi, Aki Matsunobu, Toru Sanai, Hajime Sugihara, Shuji Toda
JournalPeritoneal dialysis international : journal of the International Society for Peritoneal Dialysis (Perit Dial Int) 2011 Jul-Aug Vol. 31 Issue 4 Pg. 466-76 ISSN: 1718-4304 [Electronic] United States
PMID21532005 (Publication Type: Journal Article)
CopyrightCopyright © 2011 International Society for Peritoneal Dialysis
Chemical References
  • Dialysis Solutions
  • Mitogen-Activated Protein Kinases
Topics
  • Cells, Cultured
  • Dialysis Solutions
  • Epithelial Cells (pathology)
  • Epithelial-Mesenchymal Transition
  • Humans
  • Hyperplasia
  • Mitogen-Activated Protein Kinases (physiology)
  • Peritoneal Dialysis
  • Peritoneal Fibrosis (etiology)
  • Peritoneum (cytology)
  • Rheology
  • Stress, Mechanical

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