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World Journal of Urology
Published in: World Journal of Urology 1/2014

01-02-2014 | Original Article

Calcium oxalate nephrolithiasis and expression of matrix GLA protein in the kidneys

Authors: Aslam Khan, Wei Wang, Saeed R. Khan

Published in: World Journal of Urology | Issue 1/2014

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Abstract

Objectives

Polymorphism of the gene for matrix GLA protein (MGP), a calcification inhibitor, is associated with nephrolithiasis. However, experimental investigations of MGP role in stone pathogenesis are limited. We determined the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HA) crystal on the expression of MGP.

Methods

MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox and 33, 66 or 133–150 μg/cm2 of COM/HA for 3–72 h. MGP expression and production were determined by Western blotting and densitometric analysis. Enzyme-linked immunosorbent assay was performed to determine MGP release into the medium. Hyperoxaluria was induced in male Sprague–Dawley rats by feeding hydroxyl-l-proline. Immunohistochemistry was performed to detect renal MGP expression.

Results

Exposure to Ox and crystals led to time- and concentration-dependent increase in expression of MGP in MDCK cells. Cellular response was quicker to crystal exposure than to the Ox, expression being significantly higher after 3-h exposure to COM or HA crystals and more than 6 h of exposure to Ox. MGP expression was increased in kidneys of hyperoxaluric rats particularly in renal peritubular vessels.

Conclusion

We demonstrate increased expression of MGP in renal tubular epithelial cells exposed to Ox or CaOx crystals as well as the HA crystals. The most significant finding of this study is the increased staining seen in renal peritubular vessels of the hyperoxaluric rats, indicating involvement of renal endothelial cells in the synthesis of MGP.
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Metadata
Title
Calcium oxalate nephrolithiasis and expression of matrix GLA protein in the kidneys
Authors
Aslam Khan
Wei Wang
Saeed R. Khan
Publication date
01-02-2014
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2014
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-013-1050-2

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