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MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation

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 sho...

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Autores principales: Chen, Jun-Jiang, Wang, Yan, Meng, Xiaojing, Ruan, Ye Chun, Zou, Fei, Chan, Hsiao Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667979/
https://www.ncbi.nlm.nih.gov/pubmed/29108246
http://dx.doi.org/10.18632/oncotarget.19676
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author Chen, Jun-Jiang
Wang, Yan
Meng, Xiaojing
Ruan, Ye Chun
Zou, Fei
Chan, Hsiao Chang
author_facet Chen, Jun-Jiang
Wang, Yan
Meng, Xiaojing
Ruan, Ye Chun
Zou, Fei
Chan, Hsiao Chang
author_sort Chen, Jun-Jiang
collection PubMed
description 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 PGE(2) release 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/PGE(2) signaling essential to embryo implantation with implication in cancer progression as well.
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spelling pubmed-56679792017-11-04 MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation Chen, Jun-Jiang Wang, Yan Meng, Xiaojing Ruan, Ye Chun Zou, Fei Chan, Hsiao Chang Oncotarget Research Paper 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 PGE(2) release 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/PGE(2) signaling essential to embryo implantation with implication in cancer progression as well. Impact Journals LLC 2017-07-28 /pmc/articles/PMC5667979/ /pubmed/29108246 http://dx.doi.org/10.18632/oncotarget.19676 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Jun-Jiang
Wang, Yan
Meng, Xiaojing
Ruan, Ye Chun
Zou, Fei
Chan, Hsiao Chang
MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title_full MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title_fullStr MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title_full_unstemmed MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title_short MRP4 regulates ENaC-dependent CREB/COX-2/PGE(2) signaling during embryo implantation
title_sort mrp4 regulates enac-dependent creb/cox-2/pge(2) signaling during embryo implantation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667979/
https://www.ncbi.nlm.nih.gov/pubmed/29108246
http://dx.doi.org/10.18632/oncotarget.19676
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