title: Insulin-like growth factors inhibit podocyte apoptosis through the PI3 kinase pathway.
abstract: BACKGROUND
  Abnormal podocyte development and progressive podocyte injury have been implicated in a number of human kidney diseases. Factors necessary for regulating development and maintenance of this cell type are only beginning to emerge.
  
  
  METHODS
  To study the role of the insulin-like growth factor (IGF) system in regulating podocyte survival, we induced human fetal podocytes to undergo apoptosis. We demonstrated a significant increase in apoptosis when these cells were incubated in the presence of etoposide, as measured by DNA fragmentation and nuclear membrane condensation and blebbing.
  
  
  RESULTS
  Podocyte apoptosis was reduced to control levels when the cells were coincubated in the presence of IGF-1. We showed that the protective effect of IGFs in this cell type was mediated through the activation of the phosphatidylinositol 3'-kinase (PI3K) pathway. IGF-1 stimulation resulted in the formation of the insulin receptor substrate (IRS)-1-p85 complex, an increase in PI3 kinase activity, and activation of protein kinase B (AKT/PKB) and the bcl-2 family member bad. Incubation of the podocytes with inhibitors of the PI3 kinase pathway resulted in a loss of this IGF-1 protective effect.
  
  
  CONCLUSIONS
  These data demonstrate an important role for the IGF system in fetal podocyte survival in vitro, and suggest potential mediators to slow or alleviate the loss or damage of the podocyte in progressive renal disease.
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Bridgewater
authors.forename: Jackie
authors.initials: J
authors.lastname: Ho
authors.forename: Victor
authors.initials: V
authors.lastname: Sauro
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Matsell
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019459:Urothelium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D007334:Insulin-Like Growth Factor I; D005047:Etoposide; D019869:Phosphatidylinositol 3-Kinases