Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia.
Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia.
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DOI：
10.1038/s41598-022-10409-3
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发表时间：
2022-04-15
影响因子：
4.6
通讯作者：
Segawa, Hiroko
中科院分区：
文献类型：
--
作者：
Sasaki, Sumire;Shiozaki, Yuji;Hanazaki, Ai;Koike, Megumi;Tanifuji, Kazuya;Uga, Minori;Kawahara, Kota;Kaneko, Ichiro;Kawamoto, Yasuharu;Wiriyasermkul, Pattama;Hasegawa, Tomoka;Amizuka, Norio;Miyamoto, Ken-Ichi;Nagamori, Shushi;Kanai, Yoshikatsu;Segawa, Hiroko
肾脏II型钠依赖性无机磷酸盐（Pi）转运蛋白NaPi 2a和NaPi 2c与其他器官合作严格调节血浆Pi浓度。高Pi负荷诱导磷酸尿激素甲状旁腺激素（PTH）和成纤维细胞生长因子23（FGF 23）的表达和分泌，其增强尿Pi排泄并防止高磷酸盐血症的发作。然而，尚不清楚高Pi负荷如何增加骨骼的FGF 23分泌以及血浆Pi浓度的设定点。在这里，我们研究了跨膜蛋白174（Tmem 174）的作用，并观察到基因共表达网络在NaPi 2a和NaPi 2c功能的证据。Tmem 174位于肾近端小管中，与NaPi 2a相互作用，但不与NaPi 2c相互作用。在Tmem 174基因敲除（KO）小鼠中，血清FGF 23浓度显著增加，但未观察到Pi排泄增加和低磷血症。此外，Tmem 174-KO小鼠表现出对FGF 23和PTH施用的降低的NaPi 2a响应性。此外，膳食Pi负荷导致Tmem 174-KO小鼠中显著的高磷酸盐血症和异常NaPi 2a调节。因此，Tmem 174被认为与骨骼中的FGF 23诱导和NaPi 2a的调节相关，以防止由于高Pi负荷和肾损伤引起的血浆Pi浓度的增加。
Renal type II sodium-dependent inorganic phosphate (Pi) transporters NaPi2a and NaPi2c cooperate with other organs to strictly regulate the plasma Pi concentration. A high Pi load induces expression and secretion of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) that enhance urinary Pi excretion and prevent the onset of hyperphosphatemia. How FGF23 secretion from bone is increased by a high Pi load and the setpoint of the plasma Pi concentration, however, are unclear. Here, we investigated the role of Transmembrane protein 174 (Tmem174) and observed evidence for gene co-expression networks in NaPi2a and NaPi2c function. Tmem174 is localized in the renal proximal tubules and interacts with NaPi2a, but not NaPi2c. In Tmem174-knockout (KO) mice, the serum FGF23 concentration was markedly increased but increased Pi excretion and hypophosphatemia were not observed. In addition, Tmem174-KO mice exhibit reduced NaPi2a responsiveness to FGF23 and PTH administration. Furthermore, a dietary Pi load causes marked hyperphosphatemia and abnormal NaPi2a regulation in Tmem174-KO mice. Thus, Tmem174 is thought to be associated with FGF23 induction in bones and the regulation of NaPi2a to prevent an increase in the plasma Pi concentration due to a high Pi load and kidney injury.
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影响因子：
4.1
作者：
Andrukhova, Olena;Zeitz, Ute;Goetz, Regina;Mohammadi, Moosa;Lanske, Beate;Erben, Reinhold G.
通讯作者：
Erben, Reinhold G.
影响因子：
4.8
作者：
Giral, Hector;Lanzano, Luca;Levi, Moshe
通讯作者：
Levi, Moshe
DOI：
10.1073/pnas.182412699
发表时间：
2002-09-03
影响因子：
11.1
作者：
Hernando, N;Déliot, N;Murer, H
通讯作者：
Murer, H
DOI：
10.1073/pnas.95.9.5372
发表时间：
1998-04-28
影响因子：
11.1
作者：
Beck, L;Karaplis, AC;Tenenhouse, HS
通讯作者：
Tenenhouse, HS
DOI：
10.1152/ajpendo.00008.2006
发表时间：
2006-07-01
影响因子：
5.1
作者：
Liu, Shiguang;Zhou, Jianping;Quarles, L. Darryl
通讯作者：
Quarles, L. Darryl