Article ; Online: Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg(2+) handling.
American journal of physiology. Renal physiology
2013 Volume 305, Issue 11, Page(s) F1563–73
Abstract: ... diet. By elucidating the Mg(2+)-sensitive DCT transcriptome, new candidate genes in renal Mg(2+ ... genes were identified that are potentially involved in renal Mg(2+) handling. To confirm ... convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg(2+) handling. In recent years ...
Abstract | The kidney plays a key role in the maintenance of Mg(2+) homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg(2+) handling. In recent years, hereditary Mg(2+) transport disorders have helped to identify important players in DCT Mg(2+) homeostasis. Nevertheless, several proteins involved in DCT-mediated Mg(2+) reabsorption remain to be discovered, and a full expression profile of this complex nephron segment may facilitate the discovery of new Mg(2+)-related genes. Here, we report Mg(2+)-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 Mg(2+)-deficient or Mg(2+)-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 Mg(2+) to identify Mg(2+) 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 Mg(2+). Moreover, new genes were identified that are potentially involved in renal Mg(2+) handling. To confirm that the selected candidate genes were regulated by dietary Mg(2+) 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 Mg(2+)-deficient diet. By elucidating the Mg(2+)-sensitive DCT transcriptome, new candidate genes in renal Mg(2+) handling have been identified. |
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MeSH term(s) | Animals ; Biological Transport/genetics ; Carrier Proteins/metabolism ; Homeostasis/physiology ; Kidney Tubules, Distal/metabolism ; Magnesium/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nephrons/metabolism ; Transcriptome/genetics | |||||
Chemical Substances | Carrier Proteins ; Magnesium (I38ZP9992A) | |||||
Language | English | |||||
Publishing date | 2013-12-01 | |||||
Publishing country | United States | |||||
Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
ZDB-ID | 603837-2 | |||||
ISSN | 1522-1466 ; 0363-6127 | |||||
ISSN (online) | 1522-1466 | |||||
ISSN | 0363-6127 | |||||
DOI | 10.1152/ajprenal.00322.2013 | |||||
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Database | MEDical Literature Analysis and Retrieval System OnLINE |
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