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.
Higuchi
Shota
S
Department of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502-8585, Japan.
Kubota
Masafumi
M
Iguchi
Kazuhiro
K
Usui
Shigeyuki
S
Kiho
Tadashi
T
Hirano
Kazuyuki
K
D051400:Aquaporin 3 / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D018938:Caco-2 Cells; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051542:Hepatocyte Nuclear Factor 3-beta / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D012097:Repressor Proteins; D014158:Transcription, Genetic; D014162:Transfection
C496027:AQP3 protein, human; C496502:FOXA2 protein, human; D007328:Insulin; D012097:Repressor Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D051400:Aquaporin 3