TGF-beta signaling in renal disease.

Since discovery over a decade ago of a role for the cytokine TGF-beta as key mediator of glomerular and tubulointerstitial pathobiology in chronic kidney diseases, studies of TGF-beta signaling in the kidney have focused on the molecular biology of fibrogenesis. In recent years, glomerular and tubular epithelial cell apoptosis and cellular transdifferentiation have been proposed as putative primary pathomechanisms that may underlie progression of renal disease. This review describes evidence in support of nonlinear models and functional roles of TGF-beta signaling in mediating apoptosis and epithelial-to-mesenchymal transdifferentiation (EMT) in chronic progressive renal disease. Emphasis is placed on cell context-dependent models of TGF-beta signaling providing a conceptual framework to consolidate seemingly distinct pathomechanisms of progression of glomerular and tubulointerstitial disease.