Division of Physiology, Department of Biomedical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand.
Biodiversity Research Centre, Thailand Institute of Scientific and Technological Research, Pathumthani, Thailand.
Physiol Rep. 2022 Apr;10(7):e15247. doi: 10.14814/phy2.15247.
In the present study, we examined the systemic and direct effects of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) on duodenal, jejunal, and ileal Mg absorption. The rats were injected with FGF-23 or PTH for 5 h before collecting the duodenum, jejunum, and ileum for Mg transport analysis in Ussing chambers. The duodenum, jejunum, and ileum were directly exposed to FGF-23, PTH, or FGF-23 plus PTH with or without cell signaling inhibitors for 150 min in Ussing chambers prior to performing the Mg transport study. The small intestinal tissues were also subjected to western blot analyses for FGF receptor (FGFR), PTH receptor (PTHR), Klotho, transient receptor potential melastatin 6 (TRPM6), and cyclin as well as the cystathionine β-synthase domain divalent metal cation transport mediator 4 (CNNM4) expression. The small intestine abundantly expressed FGFR and PTHR proteins, whereas, Klotho was not expressed in rat small intestine. Systemic PTH or FGF-23 injection significantly suppressed transcellular Mg transport in the duodenum and jejunum. Direct FGF-23-, PTH-, or FGF-23 plus PTH exposure also suppressed transcellular Mg absorption in the duodenum and jejunum. There was no additional inhibitory effect of PTH and FGF-23 on intestinal Mg absorption. The inhibitory effect of PTH, FGF-23, or FGF-23 plus PTH was abolished by Gö 6850. Systemic PTH- or FGF-23-injection significantly decreased membranous TRPM6 expression, but increased cytosolic CNNM4 expression in the duodenum, jejunum, and ileum. In the present study, we propose a novel magnesiotropic action of PTH and FGF-23 by modulating small intestinal Mg absorption.
在本研究中，我们研究了甲状旁腺激素（PTH）和成纤维细胞生长因子 23（FGF-23）对十二指肠、空肠和回肠镁吸收的系统和直接作用。在收集十二指肠、空肠和回肠进行 Ussing 室镁转运分析之前，用 FGF-23 或 PTH 注射大鼠 5 小时。在 Ussing 室中，将 FGF-23、PTH 或 FGF-23 加 PTH 直接暴露于十二指肠、空肠和回肠 150 分钟，然后进行镁转运研究。还对小肠组织进行 Western blot 分析，检测 FGF 受体（FGFR）、甲状旁腺激素受体（PTHR）、Klotho、瞬时受体电位 melastatin 6（TRPM6）和细胞周期蛋白以及胱硫醚 β-合酶结构域二价金属阳离子转运介体 4（CNNM4）表达。小肠大量表达 FGFR 和 PTHR 蛋白，而 Klotho 在大鼠小肠中不表达。全身注射 PTH 或 FGF-23 显著抑制十二指肠和空肠的细胞间镁转运。直接暴露于 FGF-23、PTH 或 FGF-23 加 PTH 也抑制了十二指肠和空肠的细胞间镁吸收。PTH 和 FGF-23 对肠道镁吸收没有额外的抑制作用。PTH、FGF-23 或 FGF-23 加 PTH 的抑制作用被 Gö 6850 消除。全身注射 PTH 或 FGF-23 显著降低了十二指肠、空肠和回肠的膜 TRPM6 表达，但增加了细胞浆 CNNM4 表达。在本研究中，我们提出了 PTH 和 FGF-23 通过调节小肠镁吸收来发挥新的镁调节作用。
