Transcriptional regulation of aquaporin 3 by insulin.

In the current study, we identified a regulatory factor for the transcription of aquaporin 3 (AQP3) whose expression is repressed by insulin. We constructed a luciferase reporter vector containing bp −1382 to −12 of the 5′-flanking region of the AQP3 gene for a reporter gene assay and observed that luciferase activity in transfectants with the plasmid decreased on treatment with insulin. Serial deletion constructs revealed two regions responsible for the insulin-mediated repression, one between bps −1382 and −780, and the other between bps −404 and −82. mRNA expression of forkhead box a2 (Foxa2), the binding site of which was located between bps −1382 and −780, was found to decrease on treatment with insulin. A mutant reporter plasmid with an altered Foxa2-binding site and siRNA for the Foxa2 sequence counteracted the insulin-mediated repression of AQP3 transcription. These results suggest that Foxa2 is one of the transcriptional regulators for AQP3 gene expression regulated by insulin. J. Cell. Biochem. 102: 1051–1058, 2007. © 2007 Wiley-Liss, Inc.