Deleting the TGF-β Receptor Attenuates Acute Proximal Tubule Injury

被引：71
作者：
Gewin, Leslie [1 ,2 ]
Vadivelu, Sangeetha [2 ]
Neelisetty, Surekha [2 ]
Srichai, Manakan B. [2 ]
Paueksakon, Paisit [3 ]
Pozzi, Ambra [1 ,2 ,4 ,5 ]
Harris, Raymond C. [1 ,2 ,5 ]
Zent, Roy [1 ,2 ,4 ,6 ]
机构：
[1] Vet Affairs Hosp, Tennessee Valley Healthcare Syst, Dept Res, Nashville, TN USA
[2] Vanderbilt Univ Sch Med, Dept Med, Div Nephrol, Nashville, TN USA
[3] Vanderbilt Univ Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN USA
[4] Vanderbilt Univ Sch Med, Dept Canc Biol, Nashville, TN USA
[5] Vanderbilt Univ Sch Med, Dept Mol Physiol & Biophys, Nashville, TN USA
[6] Vanderbilt Univ Sch Med, Dept Cell & Dev Biol, Nashville, TN USA
来源：
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2012年 / 23卷 / 12期
关键词：
GROWTH-FACTOR-BETA; ACCELERATES RECOVERY; INDUCED APOPTOSIS; RENAL ISCHEMIA; KIDNEY; PROTECTS; MICE; EXPRESSION; REGENERATION; HEPATOCYTES;
D O I：
10.1681/ASN.2012020139
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
TGF-beta 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-beta and its receptors. To determine how TGF-beta signaling in this tubular segment affects the response to AKI, we selectively deleted the TGF-beta 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-beta 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-beta signaling in the proximal tubule has a detrimental effect on the response to AKI as a result of its proapoptotic effects.
引用
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页码：2001 / 2011
页数：11
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