Decorin Deficiency Enhances Progressive Nephropathy in Diabetic Mice
Authors Kevin Jon Williams, Gang Qiu, Hitomi Katoaka Usui, Stephen R. Dunn, Peter McCue,
Erwin Bottinger, Renato V. Iozzo, Kumar Sharma
Submitted By Kumar Sharma on 11/3/2006
Status Published
Journal The American journal of pathology
Year 2007
Date Published 11/1/2007
Volume : Pages 171(5) : 1441 - 1450
PubMed Reference 17884968
Abstract Decorin, a proteoglycan that inhibits active TGF-ß, is increased in diabetic
nephropathy, however its functional significance is unclear. In this study, we
used low-dose streptozotocin to induce type 1 diabetes in wild-type (C57BL/6J
Dcn +/+), Dcn -/- , and Dcn +/- mice and studied the diabetic mice for 12 mos.
Decorin gene dose had no effect on severity of diabetes; however, the Dcn-/-
diabetic mice died significantly earlier than non-diabetic controls (57% vs 7.3%
mortality). Dcn +/+ diabetic mice failed to develop significant nephropathy.
However, the Dcn -/- diabetic mice developed a significant increase in both
albuminuria and HPLC- measured plasma creatinine levels. Interestingly, only the
Dcn+/- and -/- diabetic mice exhibited low plasma adiponectin levels at 10
months of diabetes, and adiponectin levels at 6 months of diabetes were
significantly lower in mice that subsequently died vs mice that survived. Dcn
-/- diabetic mice exhibited advanced glomerular lesions, including fibrin caps,
and by immunohistochemistry, Dcn -/- diabetic mice exhibited significant
increases in glomerular TGF-ß, type I collagen, macrophage infiltration, and
Nox4. We conclude that decorin is a natural protective factor against diabetic
nephropathy and that the Dcn -/- diabetic mouse is a useful new model of
progressive diabetic nephropathy.


Investigators with authorship
NameInstitution
Erwin BottingerMount Sinai School of Medicine
Kumar SharmaUniversity of California San Diego

Complications









Genes
SymbolDescription
Dcndecorin
Ltbp1latent transforming growth factor beta binding protein 1
Tgfb1transforming growth factor, beta 1
Tgfbr1transforming growth factor, beta receptor I
Nox4NADPH oxidase 4
Adipoqadiponectin, C1Q and collagen domain containing