The many talents of transforming growth factor-β in the kidney

Purpose of review Preclinical data suggests that transforming growth factor-beta (TGF-beta) is arguably the most potent profibrotic growth factor in kidney injury. Despite this, recent clinical trials targeting TGF-beta have been disappointing. These negative studies suggest that TGF-beta signaling in the injured kidney might be more complicated than originally thought. This review examines recent studies that expand our understanding of how this pleiotropic growth factor affects renal injury. Recent findings There are recent studies showing new mechanisms whereby TGF-beta can mediate injury (e.g. epigenetic effects, macrophage chemoattractant). However, more significant are the increasing reports on cross-talk between TGF-beta signaling and other pathways relevant to renal injury such as Wnt/beta-catenin, YAP/TAZ (transcriptional coactivator with PDZ-binding motif), and klotho/FGF23. TGF-beta clearly alters the response to injury, not just by direct transcriptional changes on target cells, but also through effects on other signaling pathways. In T cells and tubular epithelial cells, some of these TGF-beta-mediated changes are potentially beneficial. Summary It is unlikely that inhibition of TGF-beta per se will be a successful antifibrotic strategy, but a better understanding of TGF-beta's actions may reveal promising downstream targets or modulators of signaling to target therapeutically for chronic kidney disease.