Decreased renal expression of the putative calcium oxalate inhibitor Tamm-Horsfall protein in the ethylene glycol rat model of calcium oxalate urolithiasis.
Decreased renal expression of the putative calcium oxalate inhibitor Tamm-Horsfall protein in the ethylene glycol rat model of calcium oxalate urolithiasis.
复制标题
DOI：
10.1016/s0022-5347(05)65127-0
复制
发表时间：
2002-05-01
影响因子：
6.6
通讯作者：
Yang, LZ
中科院分区：
文献类型：
--
作者：
Marengo, SR;Chen, DHC;Yang, LZ
目的：Tamm-Horsfall蛋白被认为能抑制草酸钙的结晶、聚集或与肾上皮细胞的黏附。我们确定乙二醇性尿结石是否会改变肾脏和尿液Tamm-Horsfall蛋白的表达。为了比较，另一种草酸钙抑制物骨桥蛋白的表达也被分析。材料和方法：雄性大鼠给予0.75%乙二醇加AIN-76饮食(乙二醇组)(乙二醇组)或标准大鼠饮食加水(对照组)长达8周(每组6只，持续8周，每组3只，持续3天至6周)。结果：乙二醇组大鼠肾脏Tamm-Horsfall蛋白信息和蛋白(膜结合态)减少，骨桥蛋白表达增加。免疫组织化学结果显示，在乙二醇组和对照组大鼠肾小管中，Tamm-Horsfall蛋白和骨桥蛋白持续存在。尿液中表达游离形式的Tamm-Horsfall蛋白(约75 kDa)。降低，但在乙二醇组大鼠中可检测到。尽管在组织中很容易检测到骨桥蛋白，但在对照组或乙二醇组大鼠的尿液中没有检测到骨桥蛋白。在时间进程实验中，Tamm-Horsfall蛋白直到4周时才减少，此时在处理组大鼠的肾脏中可检测到草酸钙晶体。结论：与骨桥蛋白等其他草酸钙抑制剂不同，乙二醇组大鼠肾组织Tamm-Horsfall蛋白表达减少。Tamm-Horsfall蛋白的表达直到肾脏中的晶体聚集物沉积后才减少，而骨桥蛋白的表达几乎立即开始增加。通过RNA或蛋白质印迹分析和免疫化学获得的肾脏和尿液数据的比较，强调了通过多种技术检查组织和尿液的必要性，以获得对特定治疗如何改变蛋白质表达的最准确评估。
Purpose: Tamm-Horsfall protein is believed to inhibit calcium oxalate crystallization, aggregation or adhesion to the renal epithelium. We determined whether ethylene glycol induced urolithiasis changes the expression of renal and urinary Tamm-Horsfall protein. For comparison the expression of another calcium oxalate inhibitor, osteopontin, was also analyzed.Materials and Methods: Male rats were treated with 0.75% ethylene glycol plus an AIN-76 diet (Dvets, Bethlehem Pennsylvania) (ethylene glycol group,) or standard rat chow and water (control group) for up to 8 weeks (6 per group for 8 weeks and 3 per group for 3 days to 6 weeks). Kidneys and urine (8 weeks only) were harvested and analyzed by Northern and Western blot analysis, and immunohistochemistry.Results: Tamm-Horsfall protein message and protein (membrane bound form) were decreased, while those of osteopontin were increased in the kidneys of rats treated with ethylene glycol for 8 weeks. As judged by immunochemistry Tamm-Horsfall protein and osteopontin were consistently present in a few tubules in rats in the ethylene glycol and control groups, respectively. In urine expression of the free form of Tamm-Horsfall protein (approximately 75 kDa.) was decreased but detectable in ethylene glycol treated rats. Although readily detected in tissue, osteopontin was not detected in the urine of control or ethylene glycol treated rats. In the time course experiment Tamm-Horsfall protein did not decrease until 4 weeks, when calcium oxalate crystals were detectable in the kidneys of treated rats. In contrast, osteopontin was increased, although inconsistently, beginning at 3 days.Conclusions: Unlike other calcium oxalate inhibitors, such as osteopontin, renal message and protein for Tamm-Horsfall protein was decreased in ethylene glycol treated rats. Tamm-Horsfall protein expression did not decrease until aggregates of crystals had been deposited in the kidneys, while osteopontin expression began to increase almost immediately. Comparisons of the data on kidneys and urine obtained by RNA or protein blot analysis and immunochemistry underscore the need to examine tissue and urine by multiple techniques to obtain the most accurate assessment of how protein expression is changed by a given treatment.