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Aberrant expression of SPARC and its impact on proliferation and apoptosis in ADPKD cyst-lining epithelia

Wenjing Wang1, Changlin Mei, Bing Tang

  • 1Division of Nephrology, Center of Kidney Disease, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|January 20, 2006
PubMed
Abstract

Insights

Secreted protein acidic and rich in cysteine (SPARC) is elevated in autosomal dominant polycystic kidney disease (ADPKD). Increased SPARC expression in ADPKD renal tissue may inhibit cyst cell proliferation and induce apoptosis, suggesting a negative feedback role.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder influenced by environmental factors.
  • Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein involved in tissue remodeling and repair.
  • Investigating SPARC in ADPKD may elucidate its role in disease progression.

Purpose of the Study:

  • To analyze the expression and function of SPARC in the context of ADPKD.
  • To determine the effect of SPARC on cyst-lining epithelial cells in vitro.
  • To evaluate SPARC's potential as a modulator of ADPKD progression.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) for SPARC concentration.
  • In situ hybridization, immunohistochemistry, RT-PCR, and western blot for SPARC distribution and levels.
  • FACS and BrdU incorporation assays for apoptosis and proliferation studies.

Main Results:

  • SPARC levels were significantly higher in ADPKD renal cyst fluid, plasma, and urine compared to controls.
  • SPARC mRNA and protein were upregulated in polycystic renal tissue.
  • SPARC inhibited proliferation, induced G0/G1 cell cycle arrest, and promoted apoptosis in cyst-lining epithelial cells in vitro.

Conclusions:

  • Increased SPARC expression in ADPKD renal tissue suggests a potential negative feedback mechanism.
  • SPARC may play a protective role by limiting cyst growth and promoting cell death in ADPKD.
  • Further research into SPARC's therapeutic potential in ADPKD is warranted.

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