Activation of an new humoral factor (phosphatonin) in chronic renal failure

斯丹尼卡素(Stanniocalcin，STC)是一种由体鱼体内的Stannius小体产生的钙磷调节激素。最近报道了哺乳动物中STC的同源物(STC1)，它能刺激肾脏对磷的摄取。在这里，我们报道了从人骨肉瘤cDNA文库中克隆的第二个哺乳动物锡钙素(STC2)。STC2有302个氨基酸残基，与STC1和鳗鱼STC的同源性为34%。STC2有一个保守的N-糖基化位点，富含半胱氨酸，与其他锡钙素一样。STC2与STC1具有相同的外显子-内含子边界。转导STC2的CHO细胞的培养液抑制了Na-磷酸转运体(NAPI-3)的启动子活性，也抑制了肾细胞系(OK细胞)对磷的摄取。因此，STC2在Na-磷酸转运蛋白上的作用似乎与STC1相反。Northern印迹分析显示，在许多人类组织中存在多个转录本，其中骨骼肌和心脏中存在高水平的转录本。因此，我们克隆了一个广泛表达的新的人磷酸张力因子STC2，它抑制了肾脏Na-磷酸共转运体的表达。STC2可能是肾磷脂重吸收中的一种磷尿酸因子。

Stanniocalcin (STC) is a Ca- and phosphate regulating hormone produced by the corpuscles of Stannius in body fishes. The mammalian homologue of STC has recently been reported (STC1), which stimulates the phosphate uptake of kidney. Here we report the cloning of a second mammalian stanniocalcin (STC2) from the human osteosarcoma cDNA library. STC2 has 302 amino acid residues with 34% identity with STC1 and eel STC. STC2 has a conserved N-glycosylation site and is rich in cystines as is the case with other stanniocalcins. STC2 has the same exon-intron boundaries as STC1. The culture medium of STC2-transfected CHO cells inhibited the promoter activity of Na-phosphate cotransporter (NaPi-3) and also inhibited the phosphate uptake of a kidney cell line (OK cells). Therefore, the function of STC2 seems to be opposite to that of STC1 on Na-phosphate cotransporter. Northern blot analysis revealed multiple transcripts in number of human tissues with high levels being present in skeletal muscle and heart. Thus, we have cloned a widly expressed new human phosphatonic factor STC2 which suppressed the expression of renal Na-phosphate cotransporter. STC2 may be a phosphaturic factor in renal Pi reabsorption.