Differential growth factor-induced modulation of proteoglycans synthesized by normal human renal versus cyst-derived cells

Judith Kovacs, Frank A. Carone*, Zheng Z. Liu, Sakie Nakumara, Anil Kumar, Yashpal S. Kanwar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In polycystic kidney disease (PKD), there is an insiduous enlargement of the kidneys and dilation of the renal tubules associated with extracellular matrix (ECM) alterations. The latter include thickening of tubular basement membrane and decreased synthesis of sulfated proteoglycan (PG). Because PKD is believed to be a disorder of cell growth and deranged ECM metabolism, it is conceivable that the formation of cystic tubules may be modulated by certain growth factors (GF) that influence the synthesis of ECM glycoproteins. In this study, the effect of various GF, i.e., epidermal, hepatocyte (HGF) and transforming (TGF), and triiodothyronine on the PG synthesized by normal human kidney (NK) epithelial cells and cells derived from cysts of patients with , autosomal dominant PKD (ADPKD) was assessed. (35S) sulfate incorporation studies revealed that, among various GF, HGF and TGF-β1 had the maximal stimulatory effect on the synthesis of PG extracted from ADPKD cells. A minimal increase in the PG synthesis was observed in NK cells; however, PG synthesized under the influence of HGF or TGF-β1 were of relatively higher molecular weight, with a shift of Kav from 0.28 to 0.12, as ascertained by Sepharose-6B chromatography. PG synthesized by ADPKD cells had a Kav = 0.18, and it did not change with the GF treatment. The charge-density characteristics of PG of ADPKD cells were relatively lower than those of NK cells, and they were unaffected by HGF or TGF-β1 treatment. Interestingly, both the HGF and TGF-β1 significantly affected posttranslational modifications of PG. The HGF preferentially enhanced the synthesis of heparan sulfate-PG in both cell types, whereas TGF-β1 disproportionately stimulated the synthesis of chondroitin sulfate-PG. These data indicate that HGF and TGF-β1 selectively modulate the synthesis of PG derived from ADPKD cells, whereas the GF differentially influence the posttranslational modifications of PG in both the NK and ADPKD cells, henceforth, suggesting a potential role of GF in the pathogenesis of PKD.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalJournal of the American Society of Nephrology
Volume5
Issue number1
StatePublished - Jul 1994

Keywords

  • Growth factors
  • Polycystic kidney disease
  • Proteaglycans

ASJC Scopus subject areas

  • Nephrology

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