Downregulation of Klotho expression by dehydration

Tang C, Pathare G, Michael D, Fajol A, Eichenmuller M, Lang F. Downregulation of Klotho expression by dehydration. Am J Physiol Renal Physiol 301: F745-F750, 2011. First published July 6, 2011; doi:10.1152/ajprenal.00037.2011.-Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal tissue counteracts aging. Overexpression of Klotho substantially prolongs the life span. Klotho deficiency leads to excessive formation of 1,25(OH)(2)D-3, growth deficit, accelerated aging, and early death. Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. The present study explored the possibility that dehydration influences Klotho expression. Klotho transcript levels were determined by RT-PCR, and Klotho protein abundance was detected by Western blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in human embryonic kidney (HEK293) cells. Dehydration was followed by a significant decline of renal Klotho transcript levels and protein abundance, accompanied by an increase in plasma osmolarity as well as plasma ADH, aldosterone, and 1,25(OH)(2)D-3 levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 mu M) significantly decreased Klotho transcription and protein expression in HEK293 cells. In conclusion, the present observations disclose a powerful effect of dehydration on Klotho expression, an effect at least partially mediated by enhanced release of ADH and aldosterone.