Zinc induces hephaestin expression via a PI3K-CDX2 dependent mechanism to regulate iron transport in intestinal Caco-2 cells.

Zinc stimulates intestinal iron absorption via induction of divalent metal ion transporter (DMT1) and hephaestin (HEPH). While the increase in DMT1 is mediated via a PI3K/IPR2 axis, the mechanisms of Zn-induced HEPH expression downstream of PI3K remain elusive. In the current study we probed the role of Caudal-related homeobox transcription factor-2 (CDX2) on Zn-induced HEPH expression. Zn treatment of Caco-2 cells increased CDX2 phosphorylation and HEPH protein and mRNA expression. siRNA-silencing of CDX2 inhibited Zn-induced HEPH expression. LY294002, an antagonist of PI3K inhibited Zn-induced phosphorylation of CDX2, and downstream HEPH expression. These results suggest that increased expression of HEPH in intestinal cells following Zn treatment is mediated via a PI3K-CDX2 pathway. • Zinc stimulated CDX2 phosphorylation and hephaestin expression in Caco-2 cells. • SiRNA silencing of CDX2 abrogated the zinc induced hephaestin expression. • Antagonist of PI3K abrogated the zinc induced CDX2 phosphorylation as well as hephaestin expression. • Zinc induced hephaestin expression is mediated via a Pi3K -CDX2 dependent mechanism. [ABSTRACT FROM AUTHOR]