Decorin deficiency enhances progressive nephropathy in diabetic mice

Kevin Jon Williams, Gang Qiu, Hitomi Katoaka Usui, Stephen R. Dunn, Peter McCue, Erwin Bottinger, Renato V. Iozzo, Kumar Sharma

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Decorin, a proteoglycan that inhibits active transforming growth factor-β, 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 mice for up to 1 year of diabetes. Decorin gene dose had no effect on severity of diabetes; however, the Dcn-/- diabetic mice died significantly earlier than nondiabetic controls (57 versus 7.3% mortality). In contrast to wild-type diabetic mice, which failed to develop significant nephropathy, the Dcn-/- diabetic mice developed a significant increase in albuminuria and plasma creatinine and a concurrent decrease in circulating adiponectin levels. Interestingly, adiponectin levels at 6 months of diabetes were predictive of mortality in diabetic mice. Dcn-/- diabetic mice exhibited advanced glomerular lesions, including diffuse mesangial matrix accumulation and fibrin cap formation. By immunohistochemistry, Dcn-/- diabetic mice exhibited significant increases in glomerular transforming growth factor-β, 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.

Original languageEnglish (US)
Pages (from-to)1441-1450
Number of pages10
JournalAmerican Journal of Pathology
Volume171
Issue number5
DOIs
StatePublished - Nov 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Williams, K. J., Qiu, G., Usui, H. K., Dunn, S. R., McCue, P., Bottinger, E., Iozzo, R. V., & Sharma, K. (2007). Decorin deficiency enhances progressive nephropathy in diabetic mice. American Journal of Pathology, 171(5), 1441-1450. https://doi.org/10.2353/ajpath.2007.070079