Transcriptional Regulation of the Claudin-16 Gene by Mg2+Availability

Cellular Physiology and Biochemistry

关键词: Hypomagnesemia;    Hypermagnesemia;    Tubular Mg2+ Transport;    Promoter;    Gene Expression;    Paracellin-1;   

DOI  :  10.1159/000315090

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Renal tubular Mg²⁺ reabsorption is mediated predominantly by the tight junction channel protein claudin-16 which is encoded by the gene CLDN16. Hypermagnesemia decreases, whereas hypomagnesemia increases Mg²⁺ reabsorption. This study examines the role of claudin-16 in the adaptive response of the kidney to Mg²⁺ availability. Methods/Results Mice received a low-, normal- or high Mg²⁺ diet for up to 3 days. Mg²⁺-loaded animals displayed hypermagnesemia with increasing urine Mg²⁺/Ca²⁺ levels paralleled by a decrease in claudin-16 protein and mRNA in the kidney. Mg²⁺- deprived animals developed hypomagnesemia with decreasing urine Mg²⁺/Ca²⁺ levels associated with an increase in claudin-16 protein and mRNA abundance. Mg²⁺ depletion markedly increased and Mg²⁺ load decreased endogenous claudin-16 mRNA levels in calcium-sensing receptor-transfected HEK293 cells compared with native HEK293 cells. The effect of Mg²⁺ availability on the human CLDN16 (hCLDN16) gene promoter was examined. Using a 2.5kb hCLDN16 5′-flanking DNA sequence, we show that magnesium depletion increases and Mg²⁺ load decreases hCLDN16 promoter activity in transfected HEK293 cells. Conclusions Changes in Mg²⁺ availability may influence claudin-16 mediated Mg²⁺ transport at the transcriptional level. The possible involvement of the cell membrane bound Ca²⁺/Mg²⁺ sensing receptor or the potential role of a hypothetical Mg²⁺ response element on the CLDN16 promoter in the Mg²⁺-induced response remains to be explored.

【 授权许可】

CC BY-NC-ND