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Effect of LXR on the Renal NaPi transporters
Author(s) -
Caldas Yupanqui A,
Giral Hector,
Sutherland Eileen,
Sorribas Victor,
Blaine Judith,
Okamura Kayo,
Levi Moshe
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.661.3
Subject(s) - liver x receptor , endocrinology , medicine , kidney , chemistry , nuclear receptor , biology , biochemistry , transcription factor , gene
The Liver X Receptor (LXR) agonists have shown to modulate the lipid composition of different tissues including the vascular tissue and kidney. Since dyslipidemia has been associated with chronic kidney disease (CKD) and hyperphosphatemia is a consequence of CKD, we used both an in vitro and in vivo system to study the effect of the LXR agonists on renal NaPi cotransport protein regulation given their important role in maintaining Pi homeostasis. C57BL/6 mice fed chronically with either of the LXR agonists TO901317 and DMHCA show a reduction in the abundance of renal brush border membrane (BBM) NaPi transport proteins: 57% for NaPi‐2a, 40% for NaPi‐2c, and 30% for PiT‐2. After incubation for 24 hours with TO901317 the same effect was also observed in opossum kidney cells (OK: a cell culture model of the renal proximal tubule) in which levels of NaPi4 protein (the main type II NaPi transporter in OK cells) were reduced by 55% and Pi transport by 49%. In this cell line we have demonstrated increased nuclear expression of the endogenous LXR receptor following treatment with the LXR agonists. In addition, LXR agonists cause changes in the lipid profile and lipid content of the OK cell membrane. Our studies therefore document a novel role for the LXR agonists in modulation of renal NaPi transporters. This research was supported by NIH (3R01 AG026529) supplemental minority grant.