Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
Biomedical Research Group, School of Life Sciences, Anglia Ruskin University, Cambridge, UK.
Acta Physiol (Oxf). 2021 Jun;232(2):e13650. doi: 10.1111/apha.13650. Epub 2021 Mar 31.
Recent reports suggest that iron deficiency impacts both intestinal calcium and phosphate absorption, although the exact transport pathways and intestinal segment responsible have not been determined. Therefore, we aimed to systematically investigate the impact of iron deficiency on the cellular mechanisms of transcellular and paracellular calcium and phosphate transport in different regions of the rat small intestine.
Adult, male Sprague-Dawley rats were maintained on a control or iron-deficient diet for 2 weeks and changes in intestinal calcium and phosphate uptake were determined using the in situ intestinal loop technique. The circulating levels of the hormonal regulators of calcium and phosphate were determined by ELISA, while the expression of transcellular calcium and phosphate transporters, and intestinal claudins were determined using qPCR and western blotting.
Diet-induced iron deficiency significantly increased calcium absorption in the duodenum but had no impact in the jejunum and ileum. In contrast, phosphate absorption was significantly inhibited in the duodenum and to a lesser extent the jejunum, but remained unchanged in the ileum. The changes in duodenal calcium and phosphate absorption in the iron-deficient animals were associated with increased claudin 2 and 3 mRNA and protein levels, while levels of parathyroid hormone, fibroblast growth factor-23 and 1,25-dihydroxy vitamin D were unchanged.
We propose that iron deficiency alters calcium and phosphate transport in the duodenum. This occurs via changes to the paracellular pathway, whereby upregulation of claudin 2 increases calcium absorption and upregulation of claudin 3 inhibits phosphate absorption.
最近的报告表明，缺铁会影响肠道钙和磷酸盐的吸收，尽管确切的转运途径和负责的肠道节段尚未确定。因此，我们旨在系统研究缺铁对大鼠小肠不同区域细胞内钙和磷酸盐跨细胞和旁细胞转运的细胞机制的影响。
成年雄性 Sprague-Dawley 大鼠连续 2 周接受对照或缺铁饮食，采用原位肠袢技术测定肠道钙和磷酸盐摄取的变化。通过 ELISA 测定钙和磷酸盐的激素调节因子的循环水平，通过 qPCR 和 Western blot 测定跨细胞钙和磷酸盐转运体以及肠紧密连接蛋白的表达。
饮食诱导的缺铁显著增加了十二指肠的钙吸收，但对空肠和回肠没有影响。相比之下，铁缺乏动物的十二指肠和一定程度的空肠中磷酸盐吸收显著受到抑制，但回肠中没有变化。缺铁动物十二指肠钙和磷酸盐吸收的变化与紧密连接蛋白 2 和 3 的 mRNA 和蛋白水平增加有关，而甲状旁腺激素、成纤维细胞生长因子 23 和 1,25-二羟维生素 D 的水平没有变化。
我们提出，缺铁会改变十二指肠的钙和磷酸盐转运。这是通过细胞旁途径发生的，其中紧密连接蛋白 2 的上调增加钙吸收，而紧密连接蛋白 3 的上调抑制磷酸盐吸收。
