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Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells
T Quaschning1, M Königer, A Krämer-Guth
1Department of Medicine, University of Freiburg, Germany.
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. VLDL 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 the 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.