TGF-ß signaling in the kidney: profibrotic and protective effects.

ABSTRACT

Transforming growth factor-ß (TGF-ß) is generally considered as a central mediator of fibrotic diseases. Indeed, much focus has been placed on inhibiting TGF-ß and its downstream targets as ideal therapeutic strategies. However, pharmacological blockade of TGF-ß has not yet translated into successful therapy for humans, which may be due to pleiotropic effects of TGF-ß signaling. Equally, TGF-ß signaling as a protective response in kidney injury has been relatively underexplored. An emerging body of evidence from experimental kidney disease models indicates multifunctionality of TGF-ß capable of inducing profibrotic and protective effects. This review discusses recent advances highlighting the diverse roles of TGF-ß in promoting not only renal fibrosis but also protective responses of TGF-ß signaling. We review, in particular, growing evidence that supports protective effects of TGF-ß by mechanisms which include inhibiting inflammation and induction of autophagy. Additional detailed studies are required to fully understand the diverse mechanisms of TGF-ß actions in renal fibrosis and inflammation that will likely direct toward effective antifibrotic therapies.