TY - JOUR
T1 - Deleting the TGF-β receptor attenuates acute proximal tubule injury
AU - Gewin, Leslie
AU - Vadivelu, Sangeetha
AU - Neelisetty, Surekha
AU - Srichai, Manakan B.
AU - Paueksakon, Paisit
AU - Pozzi, Ambra
AU - Harris, Raymond C.
AU - Zent, Roy
PY - 2012
Y1 - 2012
N2 - 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 themain 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.
AB - 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 themain 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.
UR - http://www.scopus.com/inward/record.url?scp=84870552415&partnerID=8YFLogxK
U2 - 10.1681/ASN.2012020139
DO - 10.1681/ASN.2012020139
M3 - Article
C2 - 23160515
AN - SCOPUS:84870552415
SN - 1046-6673
VL - 23
SP - 2001
EP - 2011
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 12
ER -