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

Biochem Biophys Res Commun. 2022 Oct 20:626:1-7. doi: 10.1016/j.bbrc.2022.07.053. Epub 2022 Jul 30.

Abstract

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.

Keywords: CDX2; Caco-2 cells; Hephaestin; Iron; Iron transporters; PI3K; Zn; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDX2 Transcription Factor
  • Caco-2 Cells
  • Humans
  • Iron / metabolism
  • Membrane Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Zinc* / pharmacology

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • HEPH protein, human
  • Membrane Proteins
  • Iron
  • Zinc