The Role Of Secreted Protein, Acidic And Rich In Cysteine In The Pathogenesis Of Autosomal Dominant Polycystic Kidney Disease

In our study, the concentration of secreted protein, acidic and rich in cysteine (SPARC) was measured with ELISA; distribution and expression levels were measured with in situ hybridization, immunohistochemistry, real-time PCR and Western blot assays. SPARC level in the renal cyst fluid of patients with ADPKD was greater than that in the patients with simple renal cyst (SRC), and also greater than that found in the plasma and urine of patients with either ADPKD or SRC and normal subjects. SPARC mRNA and protein levels in polycystic renal tissue were greater than that in normal renal tissue. T o further investigate the role of SPARC in ADPKD in vitro, rhSPARC w as expressed and purified. Then cyst-lining epithelia were treated with rhSPARC at various concentrations in vitro. Cell cycle phase was examined by FACS analysis. Cell proliferation was studied using BrdU incorporation ELISA. Apoptosis was assessed by morphological observation and FACS apoptosis index (AI) analysis. We found SPARC could inhibit cyst-lining epithelial cell proliferation, bring about cell cycle arrest in the G₀/G₁ phase and induce apoptosis in vitro. SPARC treatment resulted in decreased mRNA levels of ClnD1 and Bcl-2, but increased mRNA level of P21^Wafl in cyst-lining epithelial cells. Our findings suggest that the increased SPARC expression in ADPKD renal tissue may provide protective feedback inhibition in ADPKD patients.