Involvement of glomerular SREBP-1c in diabetic nephropathy.

Involvement of glomerular SREBP-1c in diabetic nephropathy. Research Abstract Details 

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Involvement of glomerular SREBP-1c in diabetic nephropathy. Abstract Text:

Naomi Ishigaki,Takashi Yamamoto,Yoshio Shimizu,Kazuto Kobayashi,Shigeru Yatoh,Hirohito Sone,Akimitsu Takahashi,Hiroaki Suzuki,Kunihiro Yamagata,Nobuhiro Yamada,Hitoshi Shimano,Naomi Ishigaki,Takashi Yamamoto,Yoshio Shimizu,Kazuto Kobayashi,Shigeru Yatoh,Hirohito Sone,Akimitsu Takahashi,Hiroaki Suzuki,Kunihiro Yamagata,Nobuhiro Yamada,Hitoshi Shimano,

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 TGFbeta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47phox, p67phox, 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-1c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MES13 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy.

Involvement of glomerular SREBP-1c in diabetic nephropathy. Publishing Authors By Initials

N Ishigaki,T Yamamoto,Y Shimizu,K Kobayashi,S Yatoh,H Sone,A Takahashi,H Suzuki,K Yamagata,N Yamada,H Shimano,N Ishigaki,T Yamamoto,Y Shimizu,K Kobayashi,S Yatoh,H Sone,A Takahashi,H Suzuki,K Yamagata,N Yamada,H Shimano,

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Involvement of glomerular SREBP-1c in diabetic nephropathy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemical and biophysical research communication

VOLUME: 364

Page Numbers: 502-8

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 1090-2104

DAY: 16

MONTH: 10

YEAR: 2007

Involvement of glomerular SREBP-1c in diabetic nephropathy. Information

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LANGUAGE: eng

NlmUniqueID: 372516

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AFFILIATION: Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Country: United States

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MEDLINETA: Biochem Biophys Res Commun

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