title: Phosphatidic acid induces decidualization by stimulating Akt-PP2A binding in human endometrial stromal cells.
abstract: Decidualization of human endometrial stromal cells (hESCs) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 (PLD1) is required for cAMP-induced decidualization of hESCs. However, the mechanism by which phosphatidic acid (PA), the product of PLD1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESCs by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP1 and prolactin transcripts (P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP1 and prolactin mRNA levels (P < 0.05). Conversely, PLD1 knockdown rescued Akt phosphorylation. Binding of PP2A and Akt increased in response to cAMP or PA, suggesting that their binding is directly responsible for the inactivation of Akt during decidualization. Consistent with this observation, treatment with okadaic acid, a PP2A inhibitor, also inhibited cAMP-induced decidualization by blocking Akt dephosphorylation.
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Yun Young
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Joong Sub
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Korea.
authors.forename: Mee-Sup
authors.initials: MS
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.|Biomedical Research Institute and Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Joong-Soo
authors.initials: JS
authors.lastname: Han
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D004717:Endometrium / Q000166:cytology*; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D008875:Middle Aged; D019319:Okadaic Acid / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D010712:Phosphatidic Acids; D019319:Okadaic Acid; D011388:Prolactin; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D010739:Phospholipase D; C106801:phospholipase D1
keywords: decidualization; human endometrial stromal cells; infertility; phosphatidic acid; phospholipase D1