MRP4 regulates ENaC-dependent CREB/COX-2/PGE2signaling during embryo implantation

Jun Jiang Chen, Yan Wang, Xiaojing Meng, Yechun Ruan, Fei Zou, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)

Abstract

Multi-drug resistance protein 4 (MRP4), a potential chemotherapeutic target as well as a transporter for endogenous signaling molecules (e.g. prostaglandins), is known to be expressed in the endometrium, although its possible role(s) in the physiology of the endometrium remains unknown. Here, we show that MRP4 is upregulated at implantation window and localized to the basolateral membrane of the endometrial epithelium, the interface between the epithelium and stroma in mice. In human endometrial epithelial cells, MRP4 expression is upregulated by ENaC activation and the inhibition of MRP4 blocks ENaC-dependent PGE2release as well as phosphorylation of CREB. Intrauterine injection of MRP4 inhibitor in mice prior to implantation significantly downregulated implantation markers COX-2, Claudin4 and Lif, and reduced implantation rate. These results in together have revealed a previously undefined role of MRP4 in mediating ENaC-dependent CREB/COX-2/PGE2signaling essential to embryo implantation with implication in cancer progression as well.
Original languageEnglish
Pages (from-to)78520-78529
Number of pages10
JournalOncotarget
Volume8
Issue number45
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • COX-2
  • CREB
  • Embryo implantation
  • MRP4
  • PGE 2

ASJC Scopus subject areas

  • Oncology

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