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Mesangial cell DNA synthesis induced by hydrogen peroxide, interleukin-6, and platelet-derived growth factor: effects

R J D'Souza1, H M Phillips, H H Radeke

  • 1Renal and Clinical Biochemistry Research Laboratories, School of Postgraduate Medicine, University of Keele, North Staffordshire Hospital Centre, Stoke on Trent, UK.

Nephron
|January 1, 1996
PubMed

Insights

Prostanoids, particularly thromboxane A2, play a role in rat mesangial cell DNA synthesis stimulated by hydrogen peroxide (H2O2), interleukin-6 (IL-6), and platelet-derived growth factor (PDGF). Inhibiting prostanoid synthesis reduced cell growth, suggesting PG involvement in these pathways.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Renal Physiology

Background:

  • Rat mesangial cells (MC) are crucial for kidney function.
  • Hydrogen peroxide (H2O2), IL-6, and PDGF are implicated in MC proliferation.
  • The role of prostanoids (PG) in mediating these growth factor effects on MC is not fully understood.

Purpose of the Study:

  • To indirectly investigate the role of prostanoids (PG) in mediating rat mesangial cell (MC) DNA synthesis.
  • To determine if H2O2, IL-6, and PDGF-induced MC DNA synthesis involves PG pathways.

Main Methods:

  • Rat MC were treated with H2O2 alone or in combination with IL-6 or PDGF.
  • Prostanoid synthesis was inhibited using indomethacin or the thromboxane A2 synthetase inhibitor Dazmegrel.
  • DNA synthesis was quantified using 3H-thymidine incorporation (3H-TdR) after 72 hours.

Main Results:

  • H2O2 alone increased MC DNA synthesis by 34.7%.
  • H2O2 potentiated IL-6 and PDGF-induced DNA synthesis by 52% and 100%, respectively.
  • Indomethacin and Dazmegrel significantly suppressed H2O2-induced DNA synthesis, with reductions of 33% and 31.8% respectively, and markedly reduced responses to H2O2 combined with IL-6 or PDGF.

Conclusions:

  • Prostanoids, particularly thromboxane A2, are involved in mediating H2O2-induced rat mesangial cell DNA synthesis.
  • These findings suggest that PG pathways contribute to the mitogenic effects of H2O2, IL-6, and PDGF on MC.

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