TGF-β: the Master Regulator of Fibrosis

Key Points TGF-β acts on multiple cell types to drive fibrosis in progressive kidney disease TGF-β signals through both canonical and non-canonical pathways; TGF-β canonical signalling via Smads has a central role in the development of renal fibrosis The profibrotic actions of TGF-β are positively and negatively regulated by interactions with other signalling pathways and by noncoding RNA and epigenetic mechanisms Direct targeting of TGF-β is unlikely to be therapeutically feasible due to the involvement of TGF-β in other systems, including the immune system Greater understanding of the fibrotic pathways regulated by TGF-β has identified alternative therapeutic targets; re-establishing the balance between profibrotic Smad3 activation and antifibrotic Smad7 action is once such approach