Decreased synthesis and delayed processing of sulfated glycoproteins by cells from human polycystic kidneys

F. A. Carone*, H. Jin, S. Nakamura, Y. S. Kanwar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


BACKGROUND: In polycystic kidney disease, there is progressive distention of tubules and remodeling of an altered extracellular matrix. Recent findings indicate a defect(s) in the synthesis, post-translational modification, cellular transport, and extracellular matrix incorporation of proteoglycans in PKD that may have a fundamental role in its pathogenesis. EXPERIMENTAL DESIGN: Pulse-chase techniques and quantitative autoradiography were used to investigate in vitro the de novo synthesis and the kinetics of intracellular transport and extracellular matrix assembly of sulfated glycoproteins by epithelial cells from normal human kidneys (NK) and from cysts of autosomal dominant polycystic kidneys (ADPKD). NK and ADPKD cell monolayers were pulsed with [35S]sulfate for 150 min and chased for four intervals between 15 and 120 min. RESULTS: In ADPKD versus NK cells there was a significant reduction in the de novo synthesis of sulfated glycoproteins and, during the chase, a marked prolongation of the disappearance time for cellular sulfated glycoproteins. Transport kinetics revealed a substantial delay in processing and release of these macromolecules by the Golgi apparatus in ADPKD cells. During the chase, kinetics for the cellular transport of sulfated glycoproteins by secretory vesicles and their assembly into extracellular matrix were comparable in ADPKD and NK cells. However, the percentage of total sulfated glycoproteins incorporated into the matrix of ADPKD versus NK cell monolayers was notably diminished. CONCLUSIONS: The findings indicate that in ADPKD versus NK cell monolayers, synthesis of sulfated glycoproteins is impaired, processing of sulfated glycoproteins by the Golgi apparatus is prolonged, and assembly of these macromolecules into the extracellular matrix is reduced. These alterations may have a fundamental role in the pathogenesis of autosomal dominant polycystic kidney disease.

Original languageEnglish (US)
Pages (from-to)413-418
Number of pages6
JournalLaboratory Investigation
Issue number4
StatePublished - 1993


  • Golgi complex
  • Proteoglycans
  • Pulse-chase
  • Quantitative autoradiography

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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