TGF-β/BMP Pathways and the Podocyte

Abstract

Renal fibrosis is the major determinant in progression of acute and chronic kidney diseases. Transforming growth factor-β (TGF-β) has been shown to be an important mediator of progressive fibrosis. Several studies have implicated that TGF-β1 is involved in the tight balance of survival and apoptotic responses in podocytes that are Smad-dependent or independent. Bone morphogenic protein-7 (BMP-7), another member of the TGF-β superfamily, has to date been involved primarily in kidney development and was described as an active blocker of TGF-β-induced profibrotic effects. Here, we summarize the direct effects of these two cytokines on podocytes. We describe their involvement in podocyte survival and apoptosis pathways with the potential to modify the critical steps in podocyte apoptosis induction. Our group has analyzed the cross-talk of BMP-7 and TGF-β1 signaling in podocytes and we describe BMP-7 as a cytoprotective factor that could antagonize proapoptotic TGF-β signals. In addition, we identified various extracellular and intracellular modifiers that can influence this sensitive cross-talk. On the basis of our work and the work of others we conclude that the balance of TGF-β1 and BMP-7 signaling and involvement of extracellular and intracellular modifiers in these cascades are important parts of podocyte physiology and pathophysiology.