SPARC GENE-EXPRESSION IS REDUCED IN EARLY DIABETES-RELATED KIDNEY GROWTH

Renal enlargement is a characteristic feature of diabetes in humans an d experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are co mplex and involve changes in extracellular matrix, cell hypertrophy an d 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 expre ssion 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 glomeru li, renal interstitial cells and in blood vessels but not in tubular e pithelial cells. SPARC mRNA was decreased in diabetic rats without a c hange in the pattern of distribution. By immunofluorescence, SPARC pro tein 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 a ssociated with a reduction in SPARC mRNA and protein. In the context o f the known biological actions of SPARC, the findings in the present s tudy implicate this matrix protein in the pathogenesis of diabetes rel ated kidney growth.