Phosphatonin washout in Hyp mice proximal tubules:: evidence for posttranscriptional regulation
Phosphatonin washout in Hyp mice proximal tubules:: evidence for posttranscriptional regulation
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DOI：
10.1152/ajprenal.00217.2004
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发表时间：
2005-02-01
影响因子：
4.2
通讯作者：
Quigley, R
中科院分区：
文献类型：
--
作者：
Baum, M;Moe, OW;Quigley, R
X连锁低磷血症是佝偻病最常见的遗传形式。其特征是肾性磷酸盐消耗，导致低磷酸盐血症和不适当的正常或低血清1，25（OH）（2）维生素D水平。以前的研究已经指出，循环因子或磷酸酶抑制磷酸盐转运通过减少近端小管NaPi协同转运蛋白NaPi-2A的mRNA。本研究探讨的假设，也有NaPi-2A协同转运蛋白在Hyp小鼠近端小管的转录后调控，以及是否在Hyp小鼠磷酸盐转运缺陷持续进行体外研究时。我们发现Hyp小鼠的磷酸盐转运率低于C57/B6对照小鼠的50%。虽然磷酸盐转运在C57/B6小鼠近端小管中随着时间的推移在孵育期间保持稳定，但在Hyp近端小管中，磷酸盐转运从0.46 +/- 0.47增加到1.83 +/- 0.40 pmol中心点mm（-1）中心点min（-1）（P < 0.01），这与体外灌注的Hyp近端小管中的磷酸激素洗脱一致。在放线菌酮的存在下，仍然观察到磷酸盐转运的时间依赖性增加。使用单小管免疫组织化学，与C57/B6小鼠相比，Hyp小鼠的近端小管顶端NaPi-2A表达也减少。使用免疫组织化学，我们证明了增加顶端表达的NaPi-2A转运蛋白在近端小管灌注在体外Hyp小鼠，即使在存在浴放线菌酮。在Hyp小鼠体外灌注的近端小管中NaPi-2A转运蛋白的顶端表达的增加被秋水仙碱阻断。这些数据与Hyp小鼠中导致磷酸盐转运减少的快速可逆的转录后缺陷一致。
X-linked hypophosphatemia is the most common inherited form of rickets. It is characterized by renal phosphate wasting, leading to hypophosphatemia and an inappropriately normal or low serum level of 1,25(OH)(2) vitamin D. Previous studies have pointed to a circulating factor or phosphatonin-inhibiting phosphate transport by decreasing mRNA of the proximal tubule NaPi cotransporter NaPi-2A. The present study examined the hypothesis that there was also posttranscriptional regulation of the NaPi-2A cotransporter in Hyp mice proximal tubules and whether the phosphate transport defect in Hyp mice persisted when they were studied in vitro. We found that the rate of phosphate transport in Hyp mice was < 50% that in C57/B6 control mice. While phosphate transport remained stable during incubation with time in C57/B6 mice proximal tubules, it increased from 0.46 +/- 0.47 to 1.83 +/- 0.40 pmol center dot mm(-1) center dot min(-1) in Hyp proximal tubules ( P < 0.01) consistent with phosphatonin washout in Hyp proximal tubules perfused in vitro. This time-dependent increase in phosphate transport was still observed in the presence of cycloheximide. There was also a reduction of proximal tubule apical NaPi-2A expression from Hyp mice compared with C57/B6 mice using single-tubule immunohistochemistry. Using immunohistochemistry, we demonstrate an increase in apical expression of the NaPi-2A transporter in proximal tubules perfused in vitro in Hyp mice even in the presence of bath cycloheximide. The increase in apical expression of the NaPi-2A transporter in proximal tubules perfused in vitro in Hyp mice was blocked by colchicine. These data are consistent with a rapidly reversible posttranscriptional defect in Hyp mice causing a reduction in phosphate transport.