Abstract
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect on renal apoB accumulation, but led to modest attenuation of DN with ∼30% reduction in albuminuria; however, biglycan deficiency caused a striking elevation in TGF-β. Use of 1D11 led to sustained suppression of TGF-β for approximately 8 weeks at a time. The 1D11 treatment caused decreased renal apoB accumulation, decreased albuminuria, decreased renal hypertrophy, and improved survival, compared with the 13C4 treatment. Thus, prevention of renal apoB accumulation is protective against development of DN. Furthermore, this study demonstrates that prevention of renal apoB accumulation is a mechanism by which TGF-β inhibition is nephroprotective.
Document Type
Article
Publication Date
9-14-2017
Digital Object Identifier (DOI)
https://doi.org/10.1194/jlr.M078204
Funding Information
This work was supported by US Department of Veterans Affairs Merit Review Award BX000622 to L.R.T. and cores supported by National Institutes of Health Grant P30 GM103527.
Related Content
The online version of this article (available at http://www.jlr.org) contains a supplement.
Repository Citation
Wilson, Patricia G.; Thompson, Joel C.; Yoder, Meghan S.; Charnigo, Richard; and Tannock, Lisa R., "Prevention of Renal ApoB Retention is Protective Against Diabetic Nephropathy: Role of TGF-β Inhibition" (2017). Internal Medicine Faculty Publications. 131.
https://uknowledge.uky.edu/internalmedicine_facpub/131
Supplemental Material
Included in
Cellular and Molecular Physiology Commons, Diseases Commons, Lipids Commons, Statistics and Probability Commons
Notes/Citation Information
Published in Journal of Lipid Research, v. 58, issue 12, p. 2264-2274.
This research was originally published in the Journal of Lipid Research. Patricia G. Wilson, Joel C. Thompson, Meghan H. Yoder, Richard Charnigo, and Lisa R. Tannock. Prevention of Renal ApoB Retention is Protective Against Diabetic Nephropathy: Role of TGF-β Inhibition. J. Lipid Res. 2017; 58:2264-2274. © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
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