Control of calcium oxalate crystal structure and cell adherence by urinary macromolecules.
Control of calcium oxalate crystal structure and cell adherence by urinary macromolecules.
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DOI：
10.1111/j.1523-1755.1998.00839.x
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发表时间：
1998-04
影响因子：
19.6
通讯作者：
J. Wesson;Elaine M. Worcester;J. Wiessner;Neil S. Mandel;Jack G. Kleinman
中科院分区：
文献类型：
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作者：
J. Wesson;Elaine M. Worcester;J. Wiessner;Neil S. Mandel;Jack G. Kleinman
结晶多态性表现为肾结石中的草酸钙，我们已经提出，尿大分子诱导的草酸钙（CaOx）的优选结晶形式从一水合物（COM）到二水合物（COD）的转变减少了晶体附着在上皮细胞表面，从而潜在地抑制了肾结石发生的关键步骤。我们通过研究一水和二水晶体与肾小管细胞的结合以及大分子尿溶质对晶体结构的影响来验证这一假设的有效性。培养中生长的肾小管细胞比大小相当的二水合物晶体多结合50%的CaOx一水合物。在含有生理浓度和过饱和Ca 2+和C2 O 4（2-）的HEPES缓冲盐溶液中考察了大分子对CaOx自发成核的影响。许多天然存在的大分子，已知是抑制剂的结晶，特别是骨桥蛋白，肾钙蛋白和尿凝血酶原片段1，被发现有利于形成草酸钙二水合物在这个体外系统中，而其他聚合物不影响CaOx晶体结构。因此，对肾结石的天然防御可以包括通过大分子抑制剂对在尿中形成的优选CaOx晶体结构的影响来阻止晶体附着。
Crystal polymorphism is exhibited by calcium oxalates in nephrolithiasis, and we have proposed that a shift in the preferred crystalline form of calcium oxalate (CaOx) from monohydrate (COM) to dihydrate (COD) induced by urinary macromolecules reduces crystal attachment to epithelial cell surfaces, thus potentially inhibiting a critical step in the genesis of kidney stones. We have tested the validity of this hypothesis by studying both the binding of monohydrate and dihydrate crystals to renal tubule cells and the effect of macromolecular urinary solutes on crystal structure. Renal tubule cells grown in culture bound 50% more CaOx monohydrate than dihydrate crystals of comparable size. The effects of macromolecules on the spontaneous nucleation of CaOx were examined in HEPES-buffered saline solutions containing Ca2+ and C2O4(2-) at physiologic concentrations and supersaturation. Many naturally occurring macromolecules known to be inhibitors of crystallization, specifically osteopontin, nephrocalcin and urinary prothrombin fragment 1, were found to favor the formation of calcium oxalate dihydrate in this in vitro system, while other polymers did not affect CaOx crystal structure. Thus, the natural defense against nephrolithiasis may include impeding crystal attachment by an effect of macromolecular inhibitors on the preferred CaOx crystal structure that forms in urine.