Mediators of diabetic renal disease:: The case for TGF-β as the major mediator

被引:374
作者
Ziyadeh, FN [1 ]
机构
[1] Univ Penn, Penn Ctr Mol Studies Kidney Dis, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2004年 / 15卷 / 01期
关键词
D O I
10.1097/01.ASN.0000093460.24823.5B
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
The critical role of hyperglycemia in the genesis of diabetic nephropathy has been established by cell culture studies, experimental animal models, and clinical trials. Certain cytokines and growth factors have been identified as likely mediators of the effects of high ambient glucose on the kidney, but prominent among these is TGF-beta, a prototypical hypertrophic and fibrogenic cytokine. Overexpression of TGF-beta has been demonstrated in the glomerular and tubulointerstitial compartments of experimental diabetic animals. The TGF-beta receptor signaling system is also triggered, as evidenced by upregulation of the TGF-beta type II receptor and activation of the downstream Smad signaling pathway. Treatment of diabetic mice with neutralizing anti-TGF-beta antibodies prevents the development of renal hypertrophy, mesangial matrix expansion, and the decline in renal function. Antibody therapy also reverses the established lesions of diabetic glomerulopathy. These studies argue strongly in support of the hypothesis that overactivity of the TGF-beta system in the kidney is a crucial mediator of diabetic renal hypertrophy and mesangial matrix expansion.
引用
收藏
页码:S55 / S57
页数:3
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