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Phosphatidic acid induces decidualization by stimulating Akt‐ PP 2A binding in human endometrial stromal cells
Author(s) -
Lee So Young,
Lee Yun Young,
Choi Joong Sub,
Yoon MeeSup,
Han JoongSoo
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13914
Subject(s) - decidualization , stromal cell , phosphatidic acid , chemistry , microbiology and biotechnology , protein kinase b , cancer research , medicine , endocrinology , biology , phosphorylation , biochemistry , phospholipid , membrane
Decidualization of human endometrial stromal cells ( hESC s) is crucial for successful uterine implantation and maintaining pregnancy. We previously reported that phospholipase D1 ( PLD 1) is required for cAMP ‐induced decidualization of hESC s. However, the mechanism by which phosphatidic acid ( PA ), the product of PLD 1 action, might regulate decidualization is not known. We confirmed that PA induced decidualization of hESC s by observing morphological changes and measuring increased levels of decidualization markers such as IGFBP 1 and prolactin transcripts ( P < 0.05). Treatment with PA reduced phosphorylation of Akt and consequently that of FoxO1, which led to the increased IGFBP 1 and prolactin mRNA levels ( P < 0.05). Conversely, PLD 1 knockdown rescued Akt phosphorylation. Binding of PP 2A 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 PP 2A inhibitor, also inhibited cAMP ‐induced decidualization by blocking Akt dephosphorylation.