Impaired tubulogenesis of cyst-derived cells from autosomal dominant polycystic kidneys

Frank A. Carone, Sakie Nakamura, Robert Bacallao, W. James Nelson, Mustafa Khokha, Yashpal S. Kanwar

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Under approprrate growth factor or hormonal influence, renal epithelial cells cultured in collagen gels form branching tubular elements, reminiscent of metanephric tubulogenesis. This study evaluates the phenotypic characteristics of normal human renal epithelial cells (NK) and epithelial cells from cysts of autosomal dominant polycystic kidneys (ADPKD) grown in collagen gels under the influence of the growth factors (GFs) epidermal (EGF), transforming (TGF-α), hepatocyte (HGF) and fibroblast (FGF). All GFs induced cell proliferation with the formation of cell aggregates in both group of cells, however, NK cells exhibited proliferation at a much higher rate compared to ADPKD. All GFs induced formation of branching tubular elements with cell-polarity characteristics in NK cells. Such organized tubular elements were essentially absent in ADPKD cell cultures. Both NK and ADPKD cells expressed cell adhesion and matrix macromolecules. Expression of heparan sulfate-proteoglycan was diminished but enhanced for fibronectin in ADPKD cells. Receptor expression for EGF and FGF was similar. These findings indicate an impairment in tubulogenesis of ADPKD cells, perhaps related to the aberrant morphogenetic cell aggregation. Alternatively, this differentiation arrest may relate to abnormal biosynthesis of secretory matrix glycoproteins rather than those expressed on the plasmalemma.

Original languageEnglish (US)
Pages (from-to)861-868
Number of pages8
JournalKidney international
Volume47
Issue number3
DOIs
StatePublished - Mar 1995

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ASJC Scopus subject areas

  • Nephrology

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