title: Deleting the TGF-β receptor attenuates acute proximal tubule injury.
abstract: TGF-β is a profibrotic growth factor in CKD, but its role in modulating the kidney's response to AKI is not well understood. The proximal tubule epithelial cell, which is the main cellular target of AKI, expresses high levels of both TGF-β and its receptors. To determine how TGF-β signaling in this tubular segment affects the response to AKI, we selectively deleted the TGF-β type II receptor in the proximal tubules of mice. This deletion attenuated renal impairment and reduced tubular apoptosis in mercuric chloride-induced injury. In vitro, deficiency of the TGF-β type II receptor protected proximal tubule epithelial cells from hydrogen peroxide-induced apoptosis, which was mediated in part by Smad-dependent signaling. Taken together, these results suggest that TGF-β signaling in the proximal tubule has a detrimental effect on the response to AKI as a result of its proapoptotic effects.
authors.affiliation: Department of Research, Veterans Affairs Hospital, Tennessee Valley Healthcare System, Nashville, Tennessee, USA. leslie.gewin@Vanderbilt.edu
authors.forename: Leslie
authors.initials: L
authors.lastname: Gewin
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Vadivelu
authors.forename: Surekha
authors.initials: S
authors.lastname: Neelisetty
authors.forename: Manakan B
authors.initials: MB
authors.lastname: Srichai
authors.forename: Paisit
authors.initials: P
authors.lastname: Paueksakon
authors.forename: Ambra
authors.initials: A
authors.lastname: Pozzi
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D007672:Kidney Cortex / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008627:Mercuric Chloride; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D008627:Mercuric Chloride; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II