An integrative view on the role of TGF-β in the progressive tubular deletion associated with chronic kidney disease

Transforming growth factor-β (TGF-β) is a cytokine known to participate in several processes related to the development of chronic kidney disease (CKD), including tubular degeneration. This is thought to occur mainly through apoptosis and epithelial-to-mesenchymal transition (EMT) of tubule epithelial cells, which give rise to a reduction of the tubular compartment and a scarring-like, fibrotic healing process of the interstitial compartment. In vivo blockade of TGF-β action has been shown to reduce CKD-associated tubular damage. However, a direct action of TGF-β on tubule cells is controversial as the underlying mechanism. On the one hand, TGF-β is known to induce EMT of tubular cells, although its incidence in vivo can hardly explain the extent of the damage. On the other hand, a few publications have reported that TGF-β induces a mild degree of apoptosis in cultured tubular cells. This most likely reflects the consequence of the cell-cycle arrest rather than a direct pro-apoptotic effect of TGF-β. The implications of these observations are analyzed in the pathological context, where normal tubular cells do not normally proliferate, but they might divide for repair purposes. Furthermore, renal fibrosis, a TGF-β-mediated event, is integrated as a potential, indirect effect contributing to tubule deletion.