Marks Joanne, Churchill Linda J, Debnam Edward S, Unwin Robert J
Department of Physiology, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF.
J Am Soc Nephrol. 2008 Dec;19(12):2313-20. doi: 10.1681/ASN.2008030315. Epub 2008 Nov 12.
The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum. Simultaneous measurement of urinary phosphate excretion suggests that the phosphaturic action of MEPE correlates with a significant reduction in the protein levels of the renal sodium-phosphate co-transporter NaPi-IIa in the proximal convoluted tubules of the outer renal cortex, assessed by Western blotting and immunohistochemistry. This short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurred without any changes in circulating levels of parathyroid hormone, 1,25-dihydroxyvitamin D(3), or fibroblast growth factor 23. Taken together, these findings suggest that MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.
被称为磷调节素的假定体液因子在磷酸盐稳态中的作用以及肾脏和胃肠道对磷酸盐处理之间的关系尚未完全明确。基质细胞外磷酸糖蛋白（MEPE）是几种候选磷调节素之一，可促进尿磷排泄，但它是否也影响肠道磷酸盐吸收尚不清楚。在此，我们使用原位肠袢技术证明，短期输注MEPE可抑制空肠而非十二指肠的磷酸盐吸收。同时测量尿磷排泄表明，MEPE的促尿磷作用与通过蛋白质印迹法和免疫组织化学评估的肾外皮质近端曲管中肾钠-磷酸盐共转运蛋白NaPi-IIa的蛋白质水平显著降低相关。MEPE对肾脏和肠道磷酸盐处理的这种短期抑制作用发生时，甲状旁腺激素、1,25-二羟维生素D(3)或成纤维细胞生长因子23的循环水平没有任何变化。综上所述，这些发现表明MEPE是参与磷酸盐稳态的候选磷调节素，在肾脏和胃肠道中均起作用。
