Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

** High Glucose Reduces Cortical Fibroblast EPO Expression with Early Reduction in Endothelial EPO Receptor Expression

  • Siska Sumual, Renal Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards NSW 2065, Australia
  • Stella McGinn, Renal Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards NSW 2065, Australia
  • Usha Panchapakesan, Renal Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards NSW 2065, Australia
  • Carol Pollock, Renal Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards NSW 2065, Australia

    • Introduction: Diabetic nephropathy is associated with tubulointerstitial fibrosis and reduced capillary number. Renal cortical fibroblasts produce erythropoietin (EPO) a protein that influences angiogenesis and hence capillary number. Endothelial cells express EPO receptors that regulate capillary angiogenesis. The role that high glucose may play on renal EPO production and capillary EPO receptor expression, and therefore local angiogenesis has not been previously studied.
    Methods: Human cortical fibroblasts (CFs) were grown to confluence and then exposed to high glucose (25mM glucose) and osmotic control (20mM L-glucose and 5mMglucose) for 24, 48, 72 and 168 hours. EPO protein expression was measured by immunoprecipitation and Western blot. Human umbilical vein endothelial cells (HUVECs) were grown under similar experimental conditions and EPO receptor expression measured by Western blot.
    Results: One week following exposure of high glucose to CFs, a significant reduction in EPO expression (P<0.05) was observed. HUVECs exposed to high glucose reduced EPO receptor expression (P<0.05) at 48 hours but this returned to normal by 72 hours.
    Conclusion: Exposure of CFs to high glucose for prolonged periods reduces EPO production. In parallel, short term exposure of endothelial cells to high glucose exposure induces an early reduction in EPO receptor expression. The observed changes suggest that a reduction in EPO bioavailability and activity may predispose to complications in patients with diabetes mellitus, including reduced angiogenesis.

    Conference Organiser - ICMS Pty Ltd