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

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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.