人肾小球细胞通过受体介导的脂蛋白摄取：与皮肤成纤维细胞和HepG2细胞的比较。

Receptor-mediated lipoprotein uptake by human glomerular cells: comparison with skin fibroblasts and HepG2 cells.

作者信息

Quaschning T, Königer M, Krämer-Guth A, Greiber S, Pavenstädt H, Nauck M, Schollmeyer P, Wanner C

机构信息

Department of Medicine, University of Freiburg, Germany.

出版信息

Nephrol Dial Transplant. 1997 Dec;12(12):2528-36. doi: 10.1093/ndt/12.12.2528.

DOI:10.1093/ndt/12.12.2528

PMID:9430847

Abstract

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.

摘要

背景

目前肾小球脂质蓄积的机制尚未完全明确。本研究旨在阐述肾小球细胞摄取脂质的机制。由于肾脏疾病常伴有含载脂蛋白E的富含甘油三酯脂蛋白的蓄积，我们感兴趣的是研究肾小球上皮细胞或系膜细胞除了已明确的低密度脂蛋白（LDL）受体外是否还拥有极低密度脂蛋白（VLDL）受体。

方法

将125I标记的极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）在人肾小球上皮细胞和系膜细胞中的摄取动力学与具有既定受体状态的细胞（即人皮肤成纤维细胞和HepG2细胞）中的脂质摄取进行比较。

结果

肾小球上皮细胞、系膜细胞、皮肤成纤维细胞以及肝细胞均表达VLDL受体mRNA，表明它们均具有VLDL受体。肾小球上皮细胞、系膜细胞和皮肤成纤维细胞对VLDL的摄取特异性低于HepG2细胞（低25%）。LDL摄取的特异性未发现差异。VLDL对HepG2细胞中VLDL摄取的抑制作用比LDL更有效。在皮肤成纤维细胞、肾小球上皮细胞和系膜细胞中，VLDL和LDL对VLDL摄取的抑制作用相同。与HepG2细胞相比，肾小球细胞中VLDL的降解-摄取比提高了50%，表明这些细胞中存在高效的细胞内脂蛋白周转。