Urinary macromolecular inhibition of crystal adhesion to renal epithelial cells is impaired in male stone formers
Urinary macromolecular inhibition of crystal adhesion to renal epithelial cells is impaired in male stone formers
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DOI：
10.1111/j.1523-1755.2005.00595.x
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发表时间：
2005-10-01
影响因子：
19.6
通讯作者：
Lieske, JC
中科院分区：
文献类型：
--
作者：
Kumar, V;de la Vega, LP;Lieske, JC
背景在肾小管液中形成的微晶的保留可能是肾结石形成的关键事件。本研究旨在确定结石形成（SF）个体的尿大分子是否具有降低的抑制晶体粘附至肾细胞的能力。从24名SF受试者（17名男性和7名女性）和24名年龄、种族和性别匹配的对照（C）中获得第一个早晨全尿（WU）样本。将尿液等分试样离心，并将不含> 10 kD的大分子的超滤液（UF）和10 x浓缩液（U-浓度）浓缩。用增加量的U-conc补充UF以使大分子浓度恢复到基线的0.25倍、0.5倍或1倍，逐渐降低晶体与细胞的结合。与对照组相比，雄性SF组的这种效应减弱（P < 0.05，SF vs. C，UF +0.25 x大分子）。雌性组中无明显差异。为了鉴定相关的大分子，将一水草酸钙（COM）晶体用U-conc和粘附蛋白包被，然后释放并通过Western印迹进行探测。来自男性对照的包被COM晶体含有比SF受试者多3.5倍的Tamm-Horsfall蛋白（THP）（P < 0.01）。COM晶体涂层与其他蛋白质并没有一贯不同的组之间。尿凝血酶原片段1（UPTF 1，P < 0.05）和晶体粘附抑制剂（CAI，P = 0.09）包被的COM晶体与细胞的结合力降低，而骨桥蛋白（OPN，P < 0.05）包被的COM晶体与细胞的粘附力增加。> 10 kD的尿大分子包被COM晶体并阻断其与肾细胞的粘附。这种能力似乎是钝化的男性，但不是女性SF个人。多种尿蛋白可能在肾细胞-尿结晶相互作用中发挥作用，THP似乎是其中较重要的一种。
Background. Retention of microcrystals that form in tubular fluid could be a critical event in kidney stone formation. This study was performed to determine if urinary macromolecules from stone-forming (SF) individuals have reduced ability to inhibit crystal adhesion to renal cells.Methods. A first morning whole urine (WU) sample was obtained from 24 SF subjects (17 males and 7 females) and 24 age-, race-, and sex-matched controls (C). An aliquot of urine was centrifuged and an ultrafiltrate (UF) free of macromolecules > 10 kD and 10x concentrate (U-conc) were prepared.Results. Supplementing UF with increasing amounts of U-conc to return the macromolecule concentration to 0.25x, 0.5x, or 1x of baseline progressively decreased crystal binding to cells. This effect was blunted in the male SF group compared to controls (P < 0.05, SF vs. C, for UF plus 0.25x macromolecules). No difference was apparent in the female groups. In order to identify responsible macromolecule(s), calcium oxalate monohydrate (COM) crystals were coated with U-conc and adherent proteins then released and probed by Western blot. Coated COM crystals from male controls contained 3.5-fold more Tamm-Horsfall protein (THP) than SF subjects (P < 0.01). COM crystal coating with other proteins did not consistently differ between the groups. COM crystal coating by urinary prothrombin fragment 1 (UPTF1, P < 0.05) and crystal adhesion inhibitor (CAI) (P = 0.09) correlated with decreased crystal binding to cells, whereas coating with osteopontin (OPN) correlated with increased adhesion tendency (P < 0.05).Conclusion. Urinary macromolecules > 10 kD coat COM crystals and block their adhesion to renal cells. This capacity appears to be blunted in male but not female SF individuals. Multiple urinary proteins may play a role in renal cell-urinary crystal interactions, and THP appears to be one of the more important ones.