Sabbagh Yves
Sanofi-Genzyme R & D Center, Genzyme, Framingham, MA, USA.
Clin Nephrol. 2013 Jan;79(1):57-65. doi: 10.5414/CN107322.
In prokaryotes and eukaryotes inorganic phosphate plays a vital role in many cellular and biological processes. Maintenance of proper phosphate homeostasis is therefore essential and any deviation from that state can lead to several acute and chronic disease states. In order to maintain physiological levels, a tightly regulated phosphate sensing and signaling mechanism needs to exist. The earliest and best characterized mechanisms of phosphate sensing and signaling have been described in yeast and bacteria involving the Pho regulon. The Pho regulon has been shown to function in a coordinated fashion in order to meet the cellular needs of the organism. Studies have also shown that the protein kinase A (PKA) signaling pathway is involved in phosphate metabolism. In eukaryotes, due to the complexity of the regulatory mechanisms and involvement of several key regulators of phosphate secreted from different organs, it has been difficult to identify the phosphate sensor. Nonetheless the crosstalk between organs in response to phosphate provides strong evidence to support the existence of such a mechanism. This review will focus on this evidence and highlight the parallels tha exist with the Pho regulon. We will focus on the kidney-arathyroid, kidney-intestinal, parathyroid-intestinal, kidney-bone, and finally the parathyroid-bone axes.
在原核生物和真核生物中，无机磷酸盐在许多细胞和生物学过程中发挥着至关重要的作用。因此，维持适当的磷酸盐稳态至关重要，任何偏离该状态的情况都可能导致多种急性和慢性疾病状态。为了维持生理水平，需要存在一种严格调控的磷酸盐感知和信号传导机制。最早且研究最充分的磷酸盐感知和信号传导机制已在酵母和细菌中被描述，涉及 Pho 调节子。已证明 Pho 调节子以协调的方式发挥作用，以满足生物体的细胞需求。研究还表明，蛋白激酶 A（PKA）信号通路参与磷酸盐代谢。在真核生物中，由于调节机制的复杂性以及来自不同器官分泌的几种磷酸盐关键调节因子的参与，很难确定磷酸盐传感器。尽管如此，器官之间对磷酸盐的相互作用提供了有力证据支持这种机制的存在。本综述将聚焦于这一证据，并突出与 Pho 调节子存在的相似之处。我们将重点关注肾 - 甲状旁腺、肾 - 肠道、甲状旁腺 - 肠道、肾 - 骨，最后是甲状旁腺 - 骨轴。
