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Regulation of gp330/megalin expression by vitamins A and D
Author(s) -
Liu W,
Wenli Yu,
Tobias Carling,
Claes Juhlin,
Jonas Rastad,
Peter Ridefelt,
Göran Åkerström,
Per Hellman
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00253.x
Subject(s) - retinoic acid , cell culture , messenger rna , receptor , microbiology and biotechnology , biology , calcitriol receptor , chemistry , glycoprotein , retinoic acid receptor , biochemistry , gene , genetics
Background A membrane‐bound 550‐kD Ca 2+ ‐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 Ca 2+ ‐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 D 3 , 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°C, SV40 genome transcription is inhibited and the IRPTC phenotype is reversed towards non‐infected proximal tubule cells. At 41°C, gp330/megalin mRNA expression was significantly increased compared with cells incubated at 34°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.