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

慢性肾衰竭中新体液因子（磷酸钙）的激活

• 批准号: 10670999
• 负责人: MIYAMOTO Ken-ichi
• 金额: $ 1.92万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670999/
• 关键词: Stanniocalcin; Phosphatonin; Kidney; Hyphophosphatemia; Transporter; Phosphatonin; PEX; Kidney; Phosphate

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.

斯钙素（Stanniocalcin，STC）是由体鱼斯钙小体产生的一种钙磷调节激素。最近报道了STC的哺乳动物同源物（STC 1），其刺激肾脏的磷酸盐摄取。在这里，我们报告的第二个哺乳动物斯钙素（STC 2）从人骨肉瘤cDNA文库的克隆。STC 2与STC 1和鳗鱼STC具有34%的同源性，具有302个氨基酸残基。STC 2具有保守的N-糖基化位点，并且与其他斯钙素一样富含胱氨酸。STC 2具有与STC 1相同的外显子-内含子边界。STC 2转染CHO细胞的培养基抑制Na-磷酸盐协同转运蛋白（NaPi-3）的启动子活性，也抑制肾细胞系（OK细胞）的磷酸盐摄取。因此，STC 2在Na-磷酸盐协同转运蛋白上的功能似乎与STC 1相反。北方印迹分析显示在许多人体组织中存在多个转录本，其中骨骼肌和心脏中存在高水平。因此，我们克隆了一个广泛表达的新的人磷酸化因子STC 2，它抑制肾钠磷酸盐协同转运蛋白的表达。STC 2可能是肾Pi重吸收的磷酸化尿因子。

项目成果

Taketani Y: "Regulation of type II renal Na^±dependent inorganic phosphate transporters by 1,25-dihydroxyritamin D3"J.Biol.Chem.. 273. 14575-14581 (1998)

Taketani Y：“1,25-二羟基维生素D3对II型肾Na^±依赖性无机磷酸转运蛋白的调节”J.Biol.Chem.. 273. 14575-14581 (1998)

Tatsumi, S., Miyamoto, K., Kouda, T., Motonaga, K., Katai, K., Ohkido, l., Morita, K., Segawa, H., Tani, Y., Yamamoto, H., Taketani, Y. and Takeda, E.: "Identification of three isoforms for the Na+- dependent phosphate cotransporter(NaPi-2) in rat kidney.

Tatsumi, S.、Miyamoto, K.、Kouda, T.、Motonaga, K.、Katai, K.、Ohkido, l.、Morita, K.、Sekawa, H.、Tani, Y.、Yamamoto, H.、

Ishibashi K: "Molecular cloning of a second human stanniocalcin homolague(STC2)"Biochem Biophys Res Commun. 250. 252-258 (1998)

Ishibashi K：“第二个人类斯钙素同系物 (STC2) 的分子克隆”Biochem Biophys Res Commun。

Kido S., Miyamoto K., Mizobuchi H., Taketani Y., Ohkido I., Ogawa N., Kaneko Y., Harashima S., Takeda E.: "Identification of regulatory sequences and binding proteins in the type II sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate.

Kido S.、Miyamoto K.、Mizobuchi H.、Taketani Y.、Ohkido I.、Okawa N.、Kaneko Y.、Harashima S.、Takeda E.：“II 型钠/中调节序列和结合蛋白的鉴定

Taketani Y: "Regulation of type II renal Na± dependent inorganic phosphate transporters by 1.25-dinydroxy vitamin D_3"J.Biol.Chem. 273. 14575-14581 (1998)

Taketani Y：“1.25-二羟维生素 D_3 对 II 型肾 Na± 依赖性无机磷酸转运蛋白的调节”J.Biol.Chem. 273. 14575-14581 (1998)