Regulation of gp330/megalin expression by vitamins A and D

Eur J Clin Invest. 1998 Feb;28(2):100-7. doi: 10.1046/j.1365-2362.1998.00253.x.


Background: A membrane-bound 550-kD Ca2+-binding glycoprotein belonging to the low-density lipoprotein (LDL) receptor superfamily has recently been identified as a putative calcium-sensing molecule. This molecule, known as gp330/megalin, is among several tissues present in the proximal tubule, parathyroid and placental cytotrophoblasts, in which a Ca2+-sensing function has been demonstrated.

Methods: Regulation of mRNA and protein expression of gp330/megalin were studied in a recently established cell line derived from rat kidney proximal tubule cells (IRPTCs), in human JEG-3 cells and in the mouse embryonal carcinoma cell line F9.

Results: In IRPTCs, quantification of mRNA and protein expression demonstrated two- to five-fold increases after addition of 10(-6) mol L(-1) all-trans-retinoic acid, 9-cis-retinoic acid or 1,25-dihydroxyvitamin D3, alone or in combination. Similarly, an increase in gp330/megalin mRNA expression was seen in JEG-3 cells cultured with vitamin D and retinoids, as well as when F9 cells were differentiated by incubation with retinoic acid and cAMP. The IRPTCs were immortalized by viral infection with the SV40 genome preceded by a temperature-sensitive promoter. Thus, by culture of the cells at 41 degrees C, SV40 genome transcription is inhibited and the IRPTC phenotype is reversed towards non-infected proximal tubule cells. At 41 degrees C, gp330/megalin mRNA expression was significantly increased compared with cells incubated at 34 degrees C.

Conclusion: The results indicate a correlation between exposure to retinoic acid or vitamin D or induction of cell differentiation (by retinoic acid/cAMP in F9 cells or inhibition of SV40 transcription in IRPTCs) and an increase in gp330/megalin protein and mRNA expression.

MeSH terms

  • Animals
  • Blotting, Northern
  • Calcium / analysis
  • Cell Line, Transformed
  • Cytoplasm / chemistry
  • Gene Expression Regulation / drug effects
  • Heymann Nephritis Antigenic Complex
  • Humans
  • Immunohistochemistry
  • Kidney Tubules, Proximal / immunology
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Mice
  • RNA / analysis
  • RNA, Neoplasm / analysis
  • Rats
  • Staining and Labeling
  • Temperature
  • Tumor Cells, Cultured
  • Vitamin A / pharmacology*
  • Vitamin D / pharmacology*


  • Heymann Nephritis Antigenic Complex
  • Membrane Glycoproteins
  • RNA, Neoplasm
  • Vitamin A
  • Vitamin D
  • RNA
  • Calcium