What is the role of decorin in diabetic kidney disease?
The small proteoglycan decorin may intercept the activity of the TGF-beta system. Decorin administration has been advocated as potential therapy in renal fibrotic diseases, because of the findings of a relative deficiency of decorin and a relative excess of TGF-beta in acute glomerulonephritis. Does a similar situation pertain in diabetic kidney disease? Activation of TGF-beta seems to be crucial to tissue injury in diabetic nephropathy, but until recently it has not been established whether decorin plays any role in the manifestations of this disease. We review evidence that a surfeit rather than a deficit in decorin expression exists in diabetic renal disease, and that there exists a negative feed-back loop whereby TGF-beta1 induces down-regulation of decorin expression. Rat and mouse mesangial cells as well as mouse proximal tubular cells in culture exhibit increased decorin mRNA levels in high ambient glucose. Decorin mRNA level in the kidney of streptozotocin-induced diabetes in mice is rapidly and significantly increased following the induction of diabetes. Thus, the available evidence suggests that renal decorin is not deficient in this disorder and hence decorin supplementation does not seem to be warranted. Rather, interception of the effects of TGF-beta seems to be an approach most likely to yield beneficial results in diabetic nephropathy.
Mogyorósi
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A
Department of Medicine, Virginia Commonwealth University/Medical College of Virginia and McGuire VAMC, Richmond, USA.
Ziyadeh
F N
FN
D000818:Animals; D002478:Cells, Cultured; D058575:Decorin; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology
C546878:DCN protein, human; C546879:Dcn protein, mouse; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005947:Glucose