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

Hanuma Naik Ramavath, Purna Chandra Mashurabad, Puneeta Singh Yaduvanshi, Shobi Veleri, Paul A. Sharp, Raghu Pullakhandam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalBiochemical and Biophysical Research Communications
Early online date10 Aug 2022
Publication statusPublished - 20 Oct 2022


  • Caco-2 cells
  • CDX2
  • Hephaestin
  • Iron
  • Iron transporters
  • PI3K
  • siRNA
  • Zn

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