Affiliation:
1. Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; and
2. Molecular Cancer Research, UMC Utrecht, Utrecht, The Netherlands
Abstract
The kidney plays a key role in the maintenance of Mg2+ homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg2+ handling. In recent years, hereditary Mg2+ transport disorders have helped to identify important players in DCT Mg2+ homeostasis. Nevertheless, several proteins involved in DCT-mediated Mg2+ reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new Mg2+-related genes. Here, we report Mg2+-sensitive expression of the DCT transcriptome. To this end, transgenic mice expressing enhanced green fluorescent protein under a DCT-specific parvalbumin promoter were subjected to Mg2+-deficient or Mg2+-enriched diets. Subsequently, the Complex Object Parametric Analyzer and Sorter allowed, for the first time, isolation of enhanced green fluorescent protein-positive DCT cells. RNA extracts thereof were analyzed by DNA microarrays comparing high versus low Mg2+ to identify Mg2+ regulatory genes. Based on statistical significance and a fold change of at least 2, 46 genes showed differential expression. Several known magnesiotropic genes, such as transient receptor potential cation channel, subfamily M, member 6 ( Trpm6), and Parvalbumin, were upregulated under low dietary Mg2+. Moreover, new genes were identified that are potentially involved in renal Mg2+ handling. To confirm that the selected candidate genes were regulated by dietary Mg2+ availability, the expression levels of solute carrier family 41, member 3 ( Slc41a3), pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α ( Pcbd1), TBC1 domain family, member 4 ( Tbc1d4), and uromodulin ( Umod) were determined by RT-PCR analysis. Indeed, all four genes show significant upregulation in the DCT of mice fed a Mg2+-deficient diet. By elucidating the Mg2+-sensitive DCT transcriptome, new candidate genes in renal Mg2+ handling have been identified.
Publisher
American Physiological Society
Cited by
45 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Magnesium reabsorption in the kidney;American Journal of Physiology-Renal Physiology;2023-03-01
2. Magnesium Homeostasis;Clinical Journal of the American Society of Nephrology;2023-02-01
3. Functional characteristics and therapeutic potential of SLC41 transporters;Journal of Pharmacological Sciences;2023-02
4. SLC41A1 knockout mice display normal magnesium homeostasis;American Journal of Physiology-Renal Physiology;2022-11-01
5. Structural and functional comparison of magnesium transporters throughout evolution;Cellular and Molecular Life Sciences;2022-07-12