title: 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.
authors.affiliation: Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, New York; and.
authors.forename: Angara
authors.initials: A
authors.lastname: Sureshbabu
authors.affiliation: New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
authors.forename: Saif A
authors.initials: SA
authors.lastname: Muhsin
authors.affiliation: Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, New York; and mechoi@med.cornell.edu.|New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, New York.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta
keywords: BMP; Smad; TGF-β; apoptosis; autophagy; fibrosis; inflammation; kidney