Nephrology Dialysis Transplantation, Vol 12, Issue 12 2528-2536, Copyright © 1997 by Oxford University Press
T Quaschning, M Koniger, A Kramer-Guth, S Greiber, H Pavenstadt, M Nauck, P Schollmeyer and C Wanner
Background: Currently the mechanisms of glomerular
lipid accumulation are not completely understood. The present study
characterizes the mechanisms of lipid uptake by glomerular cells. Since
renal diseases are frequently associated with an accumulation of
apoE-containing triglyceride-rich lipoproteins, we were interested to
investigate whether glomerular epithelial or mesangial cells possess VLDL
receptors besides the well established LDL receptors.
Methods: Uptake kinetics of
125I-labelled very-low-density lipoproteins (VLDL)
and low-density lipoproteins (LDL) in human glomerular epithelial and
mesangial cells were compared to lipid uptake in cells with established
receptor status, i.e. human skin fibroblasts and HepG2 cells.
Results: Glomerular epithelial cells, mesangial cells,
and skin fibroblasts as well as hepatocytes express VLDL receptor mRNA,
indicating that they exhibit VLDL receptors. LDL uptake in glomerular
epithelial cells, mesangial cells and skin fibroblasts occurred with a
lower specificity than in HepG2 cells (-25%). No differences were found for
the specificity of LDL uptake. VLDL uptake in HepG2 cells was inhibited
more effectively with VLDL than with LDL. In skin fibroblasts, glomerular
epithelial and mesangial cells, VLDL and LDL were equally effective
inhibitors of VLDL uptake. The degradation-uptake ratio of VLDL in
glomerular cells was elevated 50% compared to HepG2 cells, suggesting
highly efficient intracellular lipoprotein turnover in these cells.
Conclusion: We conclude that glomerular epithelial and
mesangial cells as well as skin fibroblasts and HepG2 exhibit VLDL
receptors additionally to their LDL receptors, even though the regulation
of VLDL receptor in HepG2 cells seems to differ from the regulation in
glomerular epithelial and mesangial cells. The high
degradation-uptake-ratio in these renal cells suggests the presence of an
effective clearance pathway which might serve as protection against
lipoprotein accumulation. Key words: glomerular
epithelial cells; LDL receptor mesangial cells; VLDL receptor
ORIGINAL ARTICLES
Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells
Department of Medicine, Divisions of Nephrology and Clinical Chemistry, Universities of Freiburg and Wurzburg, Germany; Corresponding author at: Department of Medicine, Division of Nephrology, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
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