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

The Kruppel-like factor-6 (KLF-6) Regulates Epithelial-Mesenchymal Transformation (EMT) in Human Proximal Tubular Cells

  • Dr John Holian, Renal Research Group, Kolling Institute, University of Sydney, Australia
  • Dr Weier Qi, Renal Research Group, Kolling Institute, University of Sydney, Australia
  • Miss Ellein Mreich, Renal Research Group, Kolling Institute, University of Sydney, Australia
  • Darren Kelly, Australia
  • Dr Xin-Ming Chen, Kolling Institute, University of Sydney, Australia
  • Prof Carol Pollock, Renal Research Group, Kolling Institute, University of Sydney, Australia

    • Background: KLF6 is a DNA-binding protein containing zinc-finger motif and plays a key role in the regulation of cell proliferation, differentiation and development. EMT is a major contributor to the pathogenesis of renal fibrosis, as it leads to a substantial increase in the number of myofibroblasts, leading to tubular atrophy. Transforming growth factor-β1 (TGFβ1) is a key mediator of EMT. The present study is to determine the role of KLF-6 in EMT induced by TGFβ1 in proximal tubule cells.
    Methods: Following TGFβ1 treatment, E-cadherin, vimentin and the activity of MMP9 were measured as markers of EMT in wild type, KLF6 silenced (siRNA) and KLF6 over-expressed proximal tubule cells respectively using real time RT-PCR and gelatin zymography. KLF6 was also measured in kidneys of streptozotocin-induced diabetic ren-2 rats using immunohistochemical staining.
    Results: After proximal tubule cells were treated with TGFβ1 for 72 hrs, the cell morphology changed significantly, and KLF6, vimentin and the activity of MMP9 increased when compared with control (P<0.01) while E-cadherin decreased (P<0.01). KLF6 siRNA significantly reversed the effect of TGFβ1 on e-cadherin expression while over-expressed KLF6 significantly promoted the loss of e-cadherin induced by TGFβ1. High glucose significantly induced KLF6 in proximal tubule cells (P<0.01). In diabetic ren-2 rats, KLF6 increased at week 4 (P<0.05) but declined at week 16.
    Conclusion: KLF6 plays a critical role in TGFβ1-induced EMT in proximal tubule cells and in kidneys of diabetic rats and KLF6 is a potential therapeutic target in developing new strategies to arrest progressive diabetic nephropathy.

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