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What is the role of decorin in diabetic kidney disease?
1Department of Medicine, Virginia Commonwealth University/Medical College of Virginia and McGuire VAMC, Richmond, USA.
Abstract:
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.
Insights
Decorin is not deficient in diabetic kidney disease; instead, its levels increase. Therefore, decorin supplementation is not recommended for treating diabetic nephropathy.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- The small proteoglycan decorin modulates the transforming growth factor-beta (TGF-beta) system.
- Decorin deficiency and TGF-beta excess are implicated in acute glomerulonephritis.
- The role of decorin in diabetic kidney disease (DKD) has been unclear.
Purpose of the Study:
- To investigate the expression of decorin in diabetic renal disease.
- To determine if decorin supplementation is a viable therapeutic strategy for DKD.
Main Methods:
- Review of existing evidence on decorin expression in DKD.
- Analysis of decorin mRNA levels in cultured renal cells exposed to high glucose.
- Examination of decorin mRNA levels in the kidneys of mice with streptozotocin-induced diabetes.
Main Results:
- Evidence suggests a surfeit, not a deficit, of decorin in diabetic renal disease.
- A negative feedback loop exists where TGF-beta1 down-regulates decorin expression.
- Increased decorin mRNA levels were observed in cultured rat and mouse mesangial cells and mouse proximal tubular cells under high glucose conditions.
- Rapid and significant increases in kidney decorin mRNA levels were noted in mice following the induction of diabetes.
Conclusions:
- Renal decorin is not deficient in diabetic nephropathy.
- Decorin supplementation is unlikely to be beneficial for DKD.
- Interfering with TGF-beta signaling pathways may be a more promising therapeutic approach for diabetic nephropathy.