OPN induces FoxM1 expression and localization through ERK 1/2, AKT, and p38 signaling pathway in HEC-1A cells.

Yunpeng Xie,Yinghua Li,Ying Kong

doi:10.3390/ijms151223345

Yunpeng Xie, Yinghua Li + Show 1 more

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https://doi.org/10.3390/ijms151223345

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Abstract

Mammalian embryo implantation is an extremely complex process and requires endometrial receptivity. In order to establish this receptivity, sequential proliferation and differentiation during the menstrual cycle is necessary. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion and progression. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. Osteopontin (OPN), an adhesion molecule, has been studied extensively in reproduction. In this study, we observed the expression and distribution of FoxM1 during the proliferative-phase and secretory-phase human endometrium and the pre-implantation mouse uterus firstly. Then we observed the relationship between OPN and FoxM1. Our results showed that FoxM1 was mainly distributed in glandular epithelium. OPN increased the expression of FoxM1 in the human uterine epithelial cell line HEC-1A cells in a time- and concentration-dependent manner. OPN regulates FoxM1 to influence HEC-1A cell proliferation through extracellular regulated protein kinases (ERK 1/2), protein kinase B (PKB, AKT), and the p38 mitogen activated protein kinases (p38MAPK, p38) signaling pathway. Inhibition of ERK 1/2, AKT and p38 suppressed OPN-induced FoxM1 expression and location. Our data indicate that FoxM1 might be regulated by OPN to influence endometrial proliferation to establish endometrial receptivity.

Highlights

Embryo implantation is an extremely complex process, including apposition, adhesion, penetration and trophoblast invasion
We demonstrate that OPN upregulated the expression of Forkhead box M1 (FoxM1) to influence the proliferation of HEC-1A cells
Immunohistochemistry was performed to examine the distribution of FoxM1 protein in the human endometrium during the proliferative- and secretory-phases

Summary

Introduction

Embryo implantation is an extremely complex process, including apposition, adhesion, penetration and trophoblast invasion. Embryo implantation only occur during the implantation window, when the blastocyst is accepted by the maternal endometrium through mediation by adhesion molecules, immune cells, cytokines, growth factors, chemokines and so on [2]. Osteopontin (OPN) is an extracellular matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion [3], angiogenesis [4] and tumor metastasis [5]. The role of OPN has been studied extensively [6,7,8]. OPN, as one of the adhesion molecules, play a role in the various stages of blastocyst implantation [9]. OPN is expressed in glandular epithelial cells and in increasing concentrations in uterine secretions during the mid to late secretory phase [10]

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