Magnesium deficiency affects HNF1β expression in rat liver in vivo and in vitro.

Abstract

Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is involved in embryonic development and tissue-specific gene expression in several organs, including the kidney and the liver. HNF1β mutations are associated with hypomagnesemia and renal magnesium wasting; however, to date, the exact molecular mechanism involved in this regulation is unclear. Furthermore, it is not known whether the Mg concentration could per se participate to this regulation by modifying HNF1β expression. We have studied in rats the effects of a 6-week diet with deficient or supplemented Mg concentrations compared to a diet with a standard Mg concentration on HNF1β protein expression. HNF1β expression was increased in the Mg-deficient group as compared to the other groups in the liver but not in the kidney. No changes in tissue Mg level were obtained in both organs. By contrast, a significant correlation between plasma Mg concentration and HNF1β level in the rat liver was evidenced. In rat hepatocyte cultures exposed for 72h to various extracellular Mg concentrations, HNF1β expression was modified after 72h of treatment of the hepatocytes with the lowest Mg concentrations as compared to the other Mg conditions. Moreover, these changes were correlated with extracellular but not intracellular Mg concentrations. In conclusion, HNF1β expression is modified by the extracellular Mg concentration in the liver, both in vivo and in vitro, suggesting regulations with membrane events in hepatocytes.