Impaired tubulogenesis of cyst-derived cells from autosomal dominant polycystic kidneys.
Under appropriate 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-alpha), 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.
Carone
F A
FA
Department of Pathology, Northwestern University Medical School, Chicago, Illinois, USA.
Nakamura
S
S
Bacallao
R
R
Nelson
W J
WJ
Khokha
M
M
Kanwar
Y S
YS
D002448:Cell Adhesion; D002449:Cell Aggregation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017136:Ion Transport; D007684:Kidney Tubules / Q000196:embryology* / Q000378:metabolism; D008854:Microscopy, Electron; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D006133:Growth Substances; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase