Regulation of the PI3K/Akt pathway during decidualization of endometrial stromal cells

Autor: Eric Asselin, François Fabi, Sophie Parent, Laurence Tardif, Kathy Grenier, Pascal Adam, Valérie Leblanc
Rok vydání: 2016
Předmět:
0301 basic medicine
Embryology
Cellular differentiation
Peptide Hormones
AKT1
lcsh:Medicine
AKT2
Biochemistry
AKT3
Endometrium
Phosphatidylinositol 3-Kinases
Animal Cells
Medicine and Health Sciences
Phosphorylation
Post-Translational Modification
lcsh:Science
Connective Tissue Cells
Multidisciplinary
Cell Differentiation
Cell biology
Cell Motility
Connective Tissue
Cell Processes
Female
Cellular Types
Anatomy
Signal Transduction
Research Article
medicine.medical_specialty
Proteasome Endopeptidase Complex
Stromal cell
Cell Survival
Biology
Cell Line
03 medical and health sciences
Internal medicine
medicine
Humans
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
lcsh:R
Uterus
Embryos
Reproductive System
Decidualization
Biology and Life Sciences
Proteins
Cell Biology
Hormones
Prolactin
030104 developmental biology
Endocrinology
Biological Tissue
lcsh:Q
Stromal Cells
Proto-Oncogene Proteins c-akt
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 5, p e0177387 (2017)
ISSN: 1932-6203
Popis: Infertility is constantly increasing in Canada, where 16% of Canadian couples are experiencing difficulty conceiving. It is thought that infertility can emanate from the dysregulated communication between the embryo and the maternal endometrium. In order to allow for this window of implantation to be open at the right moment, endometrial stromal cells proliferate and differentiate by a mechanism called decidualization. Intracellular and molecular mechanisms involved in the regulation of apoptosis and cell proliferation during decidualization of the endometrium are yet to be fully understood. It has been well demonstrated previously that Akt is importantly involved in cell survival and glycogen synthesis. Akt1, Akt2 and Akt3 isoforms have distinct physiological roles; this could also be the case during decidualization and pregnancy. The aim of this study is to investigate the regulation of PI3K/Akt pathway during the decidualization process of endometrial stromal cells. Expression of Akt isoforms, Akt activity (phospho-Akt), pIκB and substrates of Akt during decidualization were measured. To our knowledge, these results are the first to suggest a decrease in levels of Akt isoforms as well as a downregulation of Akt activity in the process of decidualization of human endometrial stromal cells. We also uncovered that decidualization induced nuclear localization of p65 through the phosphorylation of IκB, its inhibitory subunit; however, Par-4, a recently uncovered regulator of cell differentiation, was displaced from the nucleus upon decidualization. Our results also suggest that HIESC cells exhibit decreased motility during decidualization and that PI3K pathway inhibition could be involved in this process. Finally, we demonstrate that specific Akt isoforms present unique effects on the successful induction of decidualization. Further analyses will involve investigations to understand the precise signaling mechanisms by which this pathway is regulated.
Databáze: OpenAIRE
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