TGF-β signaling in the kidney: profibrotic and protective effects
- PMID: 26739888
- PMCID: PMC4824143
- DOI: 10.1152/ajprenal.00365.2015
TGF-β signaling in the kidney: profibrotic and protective effects
Abstract
Transforming growth factor-β (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. An emerging body of evidence from experimental kidney disease models indicates multifunctionality of TGF-β capable of inducing profibrotic and protective effects. This review discusses recent advances highlighting the diverse roles of TGF-β in promoting not only 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 toward effective antifibrotic therapies.
Keywords: BMP; Smad; TGF-β; apoptosis; autophagy; fibrosis; inflammation; kidney.
Copyright © 2016 the American Physiological Society.
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