Matrix Gla protein is involved in crystal formation in kidney of hyperoxaluric rats

Abstract

Background: Matrix Gla protein (MGP) is a molecular determinant regulating vascular calcification of the extracellular matrix. However, it is still unclear how MGP may be involved in crystal formation in the kidney of hyperoxaluric rats.

Methods: Male Sprague-Dawley rats were divided into the hyperoxaluric group and control group. Hyperoxaluric rats were administrated by 0.75% ethylene glycol (EG) for up to 8 weeks. Renal MGP expression was detected by the standard avidin-biotin complex (ABC) method. Renal crystal deposition was observed by a polarizing microscope. Total RNA and protein from the rat kidney tissue were extracted. The levels of MGP mRNA and protein expression were analyzed by the real-time polymerase chain reaction (RT-PCR) and Western blot.

Results: Hyperoxaluria was induced successfully in rats. The MGP was polarly distributed, on the apical membrane of renal tubular epithelial cells, and was found in the ascending thick limbs of Henle's loop (cTAL) and the distal convoluted tubule (DCT) in hyperoxaluric rats, its expression however, was present in the medullary collecting duct (MCD) in stone-forming rats. Crystals with multilaminated structure formed in the injurious renal tubules with lack of MGP expression.MGP mRNA expression was significantly upregulated by the crystals' stimulations.

Conclusion: Our results suggested that the MGP was involved in crystals formation by the continuous expression, distributing it polarly in the renal tubular cells and binding directly to the crystals.