title: Decorin deficiency enhances progressive nephropathy in diabetic mice.
abstract: Decorin, a proteoglycan that inhibits active transforming growth factor-beta, 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-beta, 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.
authors: Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors: Kevin Jon
authors: KJ
authors: Williams
authors: Gang
authors: G
authors: Qiu
authors: Hitomi Katoaka
authors: HK
authors: Usui
authors: Stephen R
authors: SR
authors: Dunn
authors: Peter
authors: P
authors: McCue
authors: Erwin
authors: E
authors: Bottinger
authors: Renato V
authors: RV
authors: Iozzo
authors: Kumar
authors: K
authors: Sharma
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D058575:Decorin; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D013311:Streptozocin; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D024042:Collagen Type I; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D013311:Streptozocin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse