Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules
Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules
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DOI：
10.1097/01.asn.0000040593.93815.9d
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发表时间：
2003-01-01
影响因子：
13.6
通讯作者：
Hughes, J
中科院分区：
文献类型：
--
作者：
Wesson, JA;Johnson, RJ;Hughes, J
钙肾结石是肾结石病的最常见形式，其中草酸钙（CaOx）是肾结石的主要成分。目前的体外证据表明，骨桥蛋白（OPN）作为尿结晶的几种大分子抑制剂之一，在CaOx晶体形成和保留的几个阶段具有潜在的重要作用。为了确定OPN在体内的重要性，在靶向OPN基因缺失的小鼠和野生型对照小鼠中诱导高尿酸。两组均在饮用水中加入1%乙二醇（草酸盐前体），持续4周。在第4周，OPN缺陷小鼠表现出显着的CaOx晶体的小管内存款，而野生型小鼠完全不受影响。通过偏光显微镜和X射线粉末衍射分析，将组织切片中保留的晶体确定为CaOx一水合物。此外，免疫细胞化学显示，OPN野生型小鼠的高尿酸与肾OPN表达显著上调2- 4倍相关，进一步支持OPN的肾保护作用。这些数据表明，OPN作为CaOx晶体形成和保留在肾小管中的抑制剂在体内发挥关键的肾保护作用。
Calcium nephrolithiasis is the most common form of renal stone disease, with calcium oxalate (CaOx) being the predominant constituent of renal stones. Current in vitro evidence implicates osteopontin (OPN) as one of several macromolecular inhibitors of urinary crystallization with potentially important actions at several stages of CaOx crystal formation and retention. To determine the importance of OPN in vivo, hyperoxaluria was induced in mice targeted for the deletion of the OPN gene together with wild-type control mice. Both groups were given 1% ethylene glycol, an oxalate precursor, in their drinking water for up to 4 wk. At 4 wk, OPN-deficient mice demonstrated significant intratubular deposits of CaOx crystals, whereas wild-type mice were completely unaffected. Retained crystals in tissue sections were positively identified as CaOx monohydrate by both polarized optical microscopy and x-ray powder diffraction analysis. Furthermore, hyperoxaluria in the OPN wild-type mice was associated with a significant 2- to 4-fold upregulation of renal OPN expression by immunocytochemistry, lending further support to a renoprotective role for OPN. These data indicate that OPN plays a critical renoprotective role in vivo as an inhibitor of CaOx crystal formation and retention in renal tubules.