PI3 kinase and TGF-β in glomerular nephropathy: what comes first?

TGF-β and PI3K isoforms contribute to glomerular disease. In this issue of Kidney International, Finer and colleagues define a temporal and selective role for the p110γ catalytic isoform of PI3K, normally expressed by hematopoietic cells, and TGF-β in adriamycin-mediated glomerular injury. Early ectopic upregulation of p110γ by podocytes drives initial injury and proteinuria, while late upregulation of TGF-β drives fibrogenesis. Thus, proteinuria and renal fibrogenesis involve distinct signaling activated by p110γ and TGF-β, respectively.