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