Lee Justin J, Plain Allein, Beggs Megan R, Dimke Henrik, Alexander R Todd
Department of Physiology, University of Alberta, Edmonton, Canada.
The Women and Children's Health Research Institute, Edmonton, Canada.
F1000Res. 2017 Oct 3;6:1797. doi: 10.12688/f1000research.12097.1. eCollection 2017.
Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH), active vitamin D , and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.
钙和磷对于生物体内众多生理和细胞过程至关重要。因此,血浆中钙和磷的水平受到严格调控。这是通过促磷激素和促钙激素、甲状旁腺激素(PTH)、活性维生素D和成纤维细胞生长因子23(FGF23)的共同作用实现的。对此起核心作用的器官是肾脏、肠道和骨骼。在肾脏中,近端小管重吸收大部分滤过的钙和磷,分别占比超过60%和90%。负责磷回收的基本分子机制已得到充分描述,并且新出现的研究正在阐明钙透过近端肾小管上皮细胞旁通路的分子特性。大量实验工作已经阐明了PTH和FGF23对这些过程的分子作用以及它们对该肾单位段中活性维生素D合成的调节。因此,促磷激素和促钙激素对近端小管溶质转运以及随后的全身钙磷平衡的综合作用变得更加复杂。在此,我们首先回顾近端小管钙和磷重吸收的分子机制,以及作用于该段的促磷激素和促钙激素如何影响它们,然后探讨其对肾脏钙和磷处理以及全身矿物质平衡的影响。