Changes in peritoneal mesothelial cells phenotype after chronic exposure to glucose or N-acetylglucosamine

Maria Ciszewicz, George Wu, Paul Tam, Alicja Polubinska, Andrzej Brȩborowicz

Research output: Contribution to journalArticle

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Abstract

Glucose is commonly used as an osmotic solute in peritoneal dialysis fluids despite vast knowledge about deleterious peritoneal and systemic effects of that solute. N-acetylglucosamine (NAG) is a solute of the comparable size to glucose, with strong anti-inflammatory properties. We compared the chronic in vitro effect of both solutes on phenotype of peritoneal mesothelial cells. Experiments were performed of primary cultures of human peritoneal mesothelial cells, which were cultured over 4 weeks in medium supplemented either with glucose 45 mmol/L (GLU) or with NAG 45 mmol/L (NAG). Generation of reactive oxygen species (ROS) in cells was studied, as well as their ability to proliferate, synthesis of cytokines, fibronectin, and factors regulating peritoneal fibrinolysis. Cells cultured in the presence of glucose 45 mmol/L generated more ROS (+73% vs control, P <0.01), whereas NAG did not stimulate generation of ROS. GLU caused hypertrophy of mesothelial cells (+53% vs control, P <0.001) and prolonged their population doubling time (+16% vs control, P <0.01); NAG did not cause significant changes in these parameters. Healing of mesothelial monolayer after mechanical injury was impaired in GLU treated cells: (-48% vs control, P <0.001 and -40% vs NAG, P <0.05). Synthesis of Il-6, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), and fibronectin was higher in GLU group as compared with control: + 86%, P <0.001, +38%, P <0.05, +51%, P <0.001, +38%, P <0.05, respectively. In the presence of NAG, these parameters were comparable with the control group, but at the same time NAG stimulated synthesis of hyaluronan: +116% versus control, P <0.001 and + 96% versus GLU, P <0.01. Treatment with GLU resulted in decline of tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) ratio by 23% versus control, P <0.001, whereas NAG increased that parameter by 43%, P <0.01 versus control. Glucose, contrary to NAG, induces oxidative stress and proinflammatory and profibrotic changes in mesothelial cells. NAG seems to be more biocompatible osmotic solute than glucose.

Original languageEnglish (US)
Pages (from-to)337-342
Number of pages6
JournalTranslational Research
Volume150
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

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Acetylglucosamine
Phenotype
Glucose
Reactive Oxygen Species
Plasminogen Activator Inhibitor 1
Fibronectins
Oxidative stress
Dialysis
Ascitic Fluid
Peritoneal Dialysis
Fibrinolysis
Tissue Plasminogen Activator
Hyaluronic Acid
Transforming Growth Factor beta
Hypertrophy
Vascular Endothelial Growth Factor A
Cultured Cells
Monolayers
Oxidative Stress
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

Changes in peritoneal mesothelial cells phenotype after chronic exposure to glucose or N-acetylglucosamine. / Ciszewicz, Maria; Wu, George; Tam, Paul; Polubinska, Alicja; Brȩborowicz, Andrzej.

In: Translational Research, Vol. 150, No. 6, 12.2007, p. 337-342.

Research output: Contribution to journalArticle

Ciszewicz, Maria ; Wu, George ; Tam, Paul ; Polubinska, Alicja ; Brȩborowicz, Andrzej. / Changes in peritoneal mesothelial cells phenotype after chronic exposure to glucose or N-acetylglucosamine. In: Translational Research. 2007 ; Vol. 150, No. 6. pp. 337-342.
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abstract = "Glucose is commonly used as an osmotic solute in peritoneal dialysis fluids despite vast knowledge about deleterious peritoneal and systemic effects of that solute. N-acetylglucosamine (NAG) is a solute of the comparable size to glucose, with strong anti-inflammatory properties. We compared the chronic in vitro effect of both solutes on phenotype of peritoneal mesothelial cells. Experiments were performed of primary cultures of human peritoneal mesothelial cells, which were cultured over 4 weeks in medium supplemented either with glucose 45 mmol/L (GLU) or with NAG 45 mmol/L (NAG). Generation of reactive oxygen species (ROS) in cells was studied, as well as their ability to proliferate, synthesis of cytokines, fibronectin, and factors regulating peritoneal fibrinolysis. Cells cultured in the presence of glucose 45 mmol/L generated more ROS (+73{\%} vs control, P <0.01), whereas NAG did not stimulate generation of ROS. GLU caused hypertrophy of mesothelial cells (+53{\%} vs control, P <0.001) and prolonged their population doubling time (+16{\%} vs control, P <0.01); NAG did not cause significant changes in these parameters. Healing of mesothelial monolayer after mechanical injury was impaired in GLU treated cells: (-48{\%} vs control, P <0.001 and -40{\%} vs NAG, P <0.05). Synthesis of Il-6, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), and fibronectin was higher in GLU group as compared with control: + 86{\%}, P <0.001, +38{\%}, P <0.05, +51{\%}, P <0.001, +38{\%}, P <0.05, respectively. In the presence of NAG, these parameters were comparable with the control group, but at the same time NAG stimulated synthesis of hyaluronan: +116{\%} versus control, P <0.001 and + 96{\%} versus GLU, P <0.01. Treatment with GLU resulted in decline of tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) ratio by 23{\%} versus control, P <0.001, whereas NAG increased that parameter by 43{\%}, P <0.01 versus control. Glucose, contrary to NAG, induces oxidative stress and proinflammatory and profibrotic changes in mesothelial cells. NAG seems to be more biocompatible osmotic solute than glucose.",
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