Involvement of glomerular SREBP-1c in diabetic nephropathy

被引：60

作者：

Ishigaki, Naomi

Yamamoto, Takashi

Shimizu, Yoshio

Kobayashi, Kazuto

Yatoh, Shigeru

Sone, Hirohito

Takahashi, Akimitsu

Suzuki, Hiroaki

Yamagata, Kunihiro

Yamada, Nobuhiro

Shimano, Hitoshi

机构：

[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Internal Med Endocrinol & Metab, Tsukuba, Ibaraki 3058575, Japan

[2] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058575, Japan

[3] Univ Tsukuba, Inst Clin Med, Dept Nephrol, Tsukuba, Ibaraki 3058575, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 364卷 / 03期

关键词：

fatty acids; Triglycerides; diabetes; proteinuria; kidney; TGF; oxidative stress; NADPH oxidase;

D O I：

10.1016/j.bbrc.2007.10.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGF beta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47(phox), p67(phox), and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-I c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MESI3 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：502 / 508

页数：7

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