Matrix Gla Protein is Involved in Crystal Formation in Kidney of Hyperoxaluric Rats
Matrix Gla Protein is Involved in Crystal Formation in Kidney of Hyperoxaluric Rats
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DOI：
10.1159/000343396
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Xiao, Chunling
中科院分区：
文献类型：
--
作者：
Lu, Xiuli;Gao, Bing;Xiao, Chunling
背景：基质Gla蛋白（MGP）是调节血管细胞外基质钙化的分子决定簇。然而，MGP如何参与高尿酸大鼠肾脏晶体形成尚不清楚。方法：雄性SD大鼠随机分为高尿酸组和对照组。用0.75%乙二醇（EG）灌胃高尿酸大鼠8周。免疫组化ABC法检测肾组织MGP表达。偏光显微镜下观察肾脏晶体沉积。从大鼠肾组织中提取总RNA和蛋白质。采用实时荧光定量聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）检测MGP mRNA和蛋白表达水平。结果：成功诱导大鼠高尿酸血症。MGP呈极性分布，位于肾小管上皮细胞的顶膜上，在高草酸尿大鼠的亨利氏袢（cTAL）和远曲小管（DCT）的上升粗段中发现，但其表达存在于髓集合管（MCD）中结石形成大鼠。MGP表达缺失的损伤肾小管中形成具有多层结构的晶体。MGP mRNA的表达被晶体的刺激显著上调。结论：结果表明，MGP在肾小管细胞中呈极性分布，并与晶体直接结合，通过持续表达参与晶体的形成。版权所有（c）2013 S. Karger AG，巴塞尔
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 invovled 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. Copyright (c) 2013 S. Karger AG, Basel