锌通过 PI3K-CDX2 依赖的机制诱导 hephaestin 表达，从而调节肠道 Caco-2 细胞中的铁转运。

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

机构信息

Drug Safety Division, ICMR-National Institute of Nutrition, Hyderabad, India.

Department of Nutritional Sciences, Kings College London, UK.

出版信息

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

DOI:10.1016/j.bbrc.2022.07.053

PMID:35963044

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.

摘要

锌通过诱导二价金属离子转运蛋白 (DMT1) 和铁蛋白 (HEPH) 来刺激肠道铁吸收。虽然 DMT1 的增加是通过 PI3K/IPR2 轴介导的，但 PI3K 下游锌诱导的 HEPH 表达的机制仍不清楚。在本研究中，我们探讨了尾相关同源盒转录因子-2 (CDX2) 在锌诱导的 HEPH 表达中的作用。Caco-2 细胞用锌处理后，CDX2 的磷酸化和 HEPH 蛋白和 mRNA 的表达增加。CDX2 的 siRNA 沉默抑制了锌诱导的 HEPH 表达。PI3K 的拮抗剂 LY294002 抑制了锌诱导的 CDX2 的磷酸化，以及下游的 HEPH 表达。这些结果表明，锌处理后肠道细胞中 HEPH 的表达增加是通过 PI3K-CDX2 途径介导的。