Figure 1.

TGF-β signaling mediates effects on different renal compartments that may contribute to the development of CKD after AKI. TGF-β is produced by the chronically de-differentiated proximal tubule cell after renal injury. TGF-β promotes epithelial de-differentiation, cell cycle arrest, and sensitizes epithelial cells to apoptosis during injury. TGF-β signaling can shorten peritubular capillaries and reduce their patency which may promote CKD progression through worsening hypoxia. TGF-β signaling stimulates fibroblasts and pericytes to transform into myofibroblasts, potent producers of extracellular matrix, the hallmark of fibrosis. Finally, TGF-β acts as a potent chemoattractant for macrophages and may promote further injury by augmenting macrophage infiltration. One caveat is that most of these TGF-β-dependent actions were determined by genetic or pharmacologic inhibition of TGF-β signaling either before or shortly after acute injury.