Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice
Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice
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DOI：
10.1247/csf.29.91
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发表时间：
2004-12-01
影响因子：
1.5
通讯作者：
Takei, K
中科院分区：
文献类型：
--
作者：
Li, SA;Watanabe, M;Takei, K
Klotho突变小鼠（kl-/-），人类衰老的小鼠模型。在广泛的器官中表现出各种表型，包括动脉硬化、神经变性。皮肤和性腺萎缩、肺气肿、软组织钙化和认知障碍。Klotho mRNA。然而.仅在脑、肾、生殖器官、脑垂体和甲状旁腺中表达。因此，Klotho蛋白在这些有限的器官中的缺乏如何导致表型的多样性仍有待阐明。为了阐明Klotho蛋白作用于远端靶标的机制，我们检查了Klotho蛋白在脑中的定位。肾和生殖器官，并分析了KL-/-小鼠的脑和肾，以寻找这些器官中靶区域的变化。在脑中，Klotho蛋白定位于脉络丛，其中蛋白主要定位于室管膜细胞的顶端质膜。在kl-/-脑中，海马中突触的减少是明显的，表明Klotho作为脑脊液中的体液因子的作用。肾脏中的Klotho蛋白定位于远端肾小管。有趣的是，在kl-/-小鼠中，IIa型Na/磷酸盐（Pi）协同转运蛋白，其在近端肾小管重吸收磷酸盐离子中起作用。被转移了这表明，Klotho蛋白在肾脏中涉及钙稳态，其通过甲状旁腺激素（PTH）调节IIa型Na/Pi共转运蛋白的定位。Klotho蛋白在生殖器官中的表达只在成熟的生殖细胞，虽然在kl-/-小鼠生殖细胞成熟被逮捕在早期阶段。因此，Klotho蛋白不仅作为体液因子发挥作用，而且还参与激素调节。这可能解释了klotho基因突变导致多种表型的原因。
Klotho mutant mouse (kl-/-), a mouse model for human aging. exhibits various phenotypes in a wide range of organs including arteriosclerosis, neural degeneration. skin and gonadal atrophy, pulmonary emphysema, calcification of soft tissues, and cognition impairment. Klotho mRNA. however. is expressed only in brain, kidney, reproductive organs, pituitary gland, and parathyroid gland. Therefore it remains to be elucidated how lack of Klotho protein in these limited organs leads to the variery of phenotypes. To shed light on mechanisms by which Klotho protein acts on distant targets, we examined localization of Klotho protein in brain. kidney. and reproductive organs, and analyzed brain and kidney in kl-/- mice searching for changes in target regions in these organs. In brain, Klotho proteins were localized at choroid plexus, where the proteins were dominantly localized at the apical plasma membrane of ependymal cells. In kl-/- brain, reduction of synapses was evident in hippocampus, suggesting a role of Klotho as a humoral factor in cerebrospinal fluid. Klotho proteins in kidney localized at distal renal tubules. Interestingly, in kl-/- mice, type IIa Na/phosphate (Pi) cotransporters, which function at the proximal renal tubules in reabsorption of phosphate ions. were translocated. This suggests that Klotho protein in kidney is implicated in calcium homeostasis which regulates localization of type IIa Na/Pi cotransporters via parathyroid hormone (PTH). Klotho proteins in reproductive organs were expressed only in mature germ cells, although in kl-/- mice germ cell maturation was arrested at earlier stages. Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation. which may explain why mutation of klotho gene results in a variety of phenotypes.