SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE EXPRESSION AFTER SUBTOTAL NEPHRECTOMY AND BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM

Secreted protein acidic and rich in cysteine (SPARC) is an extracellul ar matrix-associated protein with antiadhesive, antiproliferative, and matrix remodeling properties. SPARC gene and protein expression were investigated after subtotal nephrectomy (STNx), a model of noninflamma tory progressive renal injury. In addition, the effect of blockade of the renin-angiotensin system by the angiotensin-converting enzyme inhi bitor ramipril or by the angiotensin II receptor antagonist valsartan was examined. The STNx rats developed hypertension, proteinuria, and r enal impairment. These changes were associated with a 2.4-fold increas e in SPARC gene expression in STNx compared with SHAM kidneys (P < 0.0 01). In situ hybridization revealed increased SPARC mRNA in glomeruli and interstitial cells, as well as de novo expression by tubular epith elial cells at sites of renal injury. Immunofluorescence studies confi rmed concordant changes in SPARC protein. Both ramipril and valsartan ameliorated renal injury and significantly reduced SPARC overexpressio n in the STNx animals. The Endings of the present study suggest that S PARC, in the context of its known biological actions, may influence so me of the pathological features associated with significant renal mass reduction.