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Cyclin I protects podocytes from apoptosis

Siân V Griffin1, J Paul Olivier, Jeffrey W Pippin

  • 1Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, 98195, USA.

The Journal of Biological Chemistry
|July 19, 2006
PubMed

Insights

Cyclin I deficiency in kidney podocytes increases their apoptosis and worsens kidney disease. Stabilizing p21(Cip1/Waf1) may protect these vital kidney cells.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Glomerular podocyte injury limits kidney regeneration, leading to glomerulosclerosis and renal failure.
  • Cyclin I is uniquely expressed in glomerular podocytes, suggesting a specific role in kidney function.

Purpose of the Study:

  • To investigate the biological function of cyclin I in glomerular podocytes.
  • To determine the role of cyclin I in podocyte apoptosis and its contribution to kidney disease.

Main Methods:

  • Generation and analysis of cyclin I knock-out ( -/- ) mice.
  • In vitro and in vivo assessment of podocyte apoptosis.
  • Experimental glomerulonephritis induction in wild-type and cyclin I -/- mice.
  • Analysis of p21(Cip1/Waf1) levels and half-life in cultured podocytes.

Main Results:

  • Cyclin I -/- podocytes exhibited increased apoptosis in vitro and in vivo.
  • Podocyte apoptosis was significantly elevated in cyclin I -/- mice following glomerulonephritis induction, correlating with reduced renal function.
  • p21(Cip1/Waf1) levels were lower and less stable in cyclin I -/- podocytes.
  • Enforced expression of p21(Cip1/Waf1) rescued cyclin I -/- podocytes from apoptosis.

Conclusions:

  • Cyclin I protects glomerular podocytes from apoptosis.
  • This protection is potentially mediated by cyclin I's role in stabilizing p21(Cip1/Waf1).
  • Targeting cyclin I or p21(Cip1/Waf1) may offer therapeutic strategies for kidney diseases involving podocyte injury.

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