CALCIUM-OXALATE MONOHYDRATE CRYSTALS ARE ENDOCYTOSED BY RENAL EPITHELIAL-CELLS AND INDUCE PROLIFERATION
CALCIUM-OXALATE MONOHYDRATE CRYSTALS ARE ENDOCYTOSED BY RENAL EPITHELIAL-CELLS AND INDUCE PROLIFERATION
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DOI：
10.1152/ajprenal.1992.262.4.f622
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发表时间：
1992-04-01
影响因子：
--
通讯作者：
TOBACK, FG
中科院分区：
文献类型：
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作者：
LIESKE, JC;WALSHREITZ, MM;TOBACK, FG
使用未转化的 BSC-1 系的猴肾上皮细胞作为模型系统，用于寻找对肾结石中常见的尿晶体的生物反应。 一水草酸钙 (COM) 是最常见的尿液晶体，它被大量内化，启动 DNA 合成，并刺激细胞增殖。 暴露于 COM 晶体后观察到的 DNA 合成增加的幅度与 10% 小牛血清相当，但发生在 8 小时后。 COM 对 DNA 合成的最大刺激与 50% 的细胞单层的晶体内吞作用相关。 COM 晶体还刺激犬肾上皮细胞（MDCK 系）的 DNA 合成和增殖。 由于 COM 刺激猴和犬肾细胞的生长，但不刺激成纤维细胞的生长，因此该晶体的促有丝分裂作用似乎具有细胞类型特异性。 羟基磷灰石还可以增强 BSC-1 细胞的增殖，而透钙磷石（另一种含钙尿晶体）却不会。 肾钙素 (NC)（正常人尿液中的一种糖蛋白，可抑制 COM 晶体的成核、聚集和生长）存在时，这些晶体启动 DNA 合成的能力被阻断。 这是首次证明特定的含钙尿晶体可以诱导肾上皮细胞增殖，而NC可以抑制这种作用。
Monkey kidney epithelial cells of the nontransformed BSC-1 line were used as a model system with which to search for biological responses to urinary crystals commonly found in renal stones. Calcium oxalate monohydrate (COM), the most common urinary crystal, was avidly internalized, initiated DNA synthesis, and stimulated cell multiplication. The increase in DNA synthesis observed after exposure to COM crystals was equivalent in magnitude to that of 10% calf serum, but occurred 8 h later. Maximal stimulation of DNA synthesis by COM was associated with crystal endocytosis by 50% of the cell monolayer. COM crystals also stimulated DNA synthesis and multiplication of canine kidney epithelial cells (MDCK line). As COM stimulated growth of both monkey and canine renal cells but not fibroblasts, the mitogenic effect of this crystal appeared cell-type specific. Hydroxyapatite also enhanced multiplication of BSC-1 cells, whereas brushite, another calcium-containing urinary crystal, did not. In the presence of nephrocalcin (NC), a glycoprotein in normal human urine that inhibits nucleation, aggregation, and growth of COM crystals, the capacity of these crystals to initiate DNA synthesis was blocked. This is the first demonstration that specific calcium-containing urinary crystals can induce proliferation of renal epithelial cells and that NC can inhibit this effect.