Insulin-like growth factor binding protein-2 modulates podocyte mitogenesis.
To study the role of insulin-like growth factors (IGF) in podocyte maturation, we isolated and characterized fetal visceral glomerular epithelial cells from human kidneys obtained at 8-18 weeks gestation. Cells were identified as podocyte lineage by their cobblestone morphology and immunoreactivity with synaptopodin, Wilms tumor-1 suppressor gene product (WT-1), complement receptor CR1, and cytoskeletal proteins smooth muscle actin and vimentin. Stimulation of the podocyte cell monolayers with IGF-II resulted in a slight increase in mitogenesis, an effect that was concentration and time dependent and abrogated by co-incubation with exogenous IGF binding protein 2 (IGFBP-2). Western blot analysis of conditioned media revealed that cultured podocytes expressed endogenous IGFBP-2 exclusively. IGF-II stimulation enhanced IGFBP-2 production in a dose- and time-dependent fashion and was associated with an increase in IGFBP-2 mRNA production. These data demonstrate that IGF-II-stimulated IGFBP-2 production appears to inhibit the mitogenic effect of IGF-II, and may have an autocrine effect on the maturation, differentiation, and survival of fetal podocytes.
Bridgewater
Darren J
DJ
Department of Anatomy and Cell Biology, University of Western Ontario, 1151 Richmond Street, N6A 5B8, London, Ontario, Canada.
Matsell
Douglas G
DG
D002469:Cell Separation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005333:Fetus / Q000166:cytology / Q000502:physiology; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000196:embryology*; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D018971:Insulin-Like Growth Factor Binding Protein 2; D011994:Recombinant Proteins; D007335:Insulin-Like Growth Factor II