Involvement of glomerular SREBP-1c in diabetic nephropathy

Journal Article · Fri Dec 21 00:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.10.038· OSTI ID:21033014

Ishigaki, Naomi; Yamamoto, Takashi ^[1]; Shimizu, Yoshio ^[2]; Kobayashi, Kazuto; Yatoh, Shigeru; Sone, Hirohito; Takahashi, Akimitsu; Suzuki, Hiroaki ^[1]; Yamagata, Kunihiro ^[2]; Yamada, Nobuhiro ^[1]; Shimano, Hitoshi ^[1]

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1. 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)
2. Department of Nephrology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki (Japan)

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 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.

• OSTI ID: 21033014
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 364, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.10.038; PII: S0006-291X(07)02179-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBOXYLIC ACIDS
GENES
GLOMERULI
HYPERGLYCEMIA
OXIDASES
OXIDATION
PROMOTERS
TRANSGENIC MICE
TRIGLYCERIDES
URINE