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SPARC gene expression is reduced in early diabetes-related kidney growth
R E Gilbert1, P G McNally, A Cox
1Endocrinology Unit, Austin Hospital, Victoria, Australia.
Abstract:
Renal enlargement is a characteristic feature of diabetes in humans and experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are complex and involve changes in extracellular matrix, cell hypertrophy and hyperplasia. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein with anti-adhesive, antiproliferative and matrix remodeling properties. We examined kidney SPARC gene expression and protein content in early experimental diabetes. By Northern blot analysis, kidney SPARC mRNA fell in diabetic animals at day 1 to 40 +/- 15% of controls levels (mean +/- SEM, P < 0.01) to 42% +/- 11% on day 3 (P < 0.01) with a further decrease at day 7 to 29 +/- 7% (P < 0.001). In situ hybridization demonstrated SPARC mRNA within glomeruli renal interstitial cells and in blood vessels but not in tubular epithelial cells. SPARC mRNA was decreased in diabetic rats within a change in the pattern of distribution. By immunofluorescence, SPARC protein was detected in glomeruli and tubular basement membrane. Diabetes was associated with a decrease in SPARC protein at both sites. These data demonstrate that the onset of diabetes-related kidney growth is associated with a reduction in SPARC mRNA and protein. In the context of the known biological actions of SPARC, the findings in the present study implicate this matrix protein in the pathogenesis of diabetes related kidney growth.
Insights
Diabetes causes kidney growth by altering extracellular matrix. This study found reduced Secreted Protein Acidic and Rich in Cysteine (SPARC) in diabetic kidneys, suggesting SPARC
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetes is linked to kidney enlargement, a predictor of renal disease.
- Diabetes-induced kidney growth involves complex extracellular matrix changes, cell hypertrophy, and hyperplasia.
- Secreted Protein Acidic and Rich in Cysteine (SPARC) is an extracellular matrix protein with known anti-adhesive, anti-proliferative, and matrix remodeling properties.
Purpose of the Study:
- To investigate the role of SPARC in the early stages of diabetes-related kidney growth.
- To examine changes in kidney SPARC gene expression and protein content during experimental diabetes.
Main Methods:
- Northern blot analysis to quantify SPARC mRNA levels.
- In situ hybridization to determine the cellular distribution of SPARC mRNA.
- Immunofluorescence to assess SPARC protein localization and levels.
Main Results:
- Kidney SPARC mRNA significantly decreased in diabetic animals compared to controls by days 1, 3, and 7.
- SPARC mRNA was detected in glomeruli, renal interstitial cells, and blood vessels, with altered distribution in diabetic rats.
- SPARC protein levels were reduced in glomeruli and tubular basement membranes of diabetic kidneys.
Conclusions:
- The onset of diabetes-related kidney growth is associated with a significant reduction in both SPARC mRNA and protein.
- These findings suggest that decreased SPARC contributes to the pathogenesis of kidney growth in diabetes.
- SPARC's role in matrix remodeling may be disrupted in diabetic nephropathy.