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Published on: May 23, 2014
Isoflavones regulate secretion of leukemia inhibitory factor and transforming growth factor {beta} and expression of
Jin-Wen Xu1, Naomi Yasui, Katsumi Ikeda
1Section of Pathophysiology, Department of Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan. jwxu@mukogawa-u.ac.jp
Abstract:
Isoflavones have attracted much attention due to their association with health benefits; however, comprehensive understanding of the beneficial impacts of isoflavones on uterine biology at the molecular level remains unexplored. In the present study, our data showed that isoflavones aglycones AglyMax, genistein, and equol, but not daidzein, within the range of plasma concentration, displayed bioavailability in regulating the secretion of leukemia inhibitory factor (LIF) and transforming growth factor beta (TGF-beta) in Ishikawa cells, which was blocked by an estrogen receptor antagonist ICI 182 780, mitogen-activated protein kinase kinase (MEK)1/2 inhibitor PD98059, and p38 mitogen-activated protein kinase inhibitor SB203580. We also found that AglyMax and genistein increased in cyclic AMP release and the expression of glycodelin protein in Ishikawa cells assayed using western blot and immunochemical staining. The MEK1/2 inhibitor PD98059 and the protein kinase A inhibitor H89, but not SB203580, attenuated this glycoprotein expression. Moreover, isoflavone aglycones AglyMax stimulated LIF, and TGF-beta secretion, and glycodelin expression in separate primary endometrial epithelial cells in the follicular phase or luteal phase from healthy subject donors. Overall, our findings suggest that isoflavones may alter the uterine expression of estrogen-responsive genes.
Insights
Isoflavone aglycones like AglyMax and genistein regulate uterine gene expression by influencing leukemia inhibitory factor (LIF) and transforming growth factor beta (TGF-beta) secretion and glycodelin protein levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Isoflavones are plant compounds with potential health benefits.
- Their specific molecular mechanisms in uterine biology are not fully understood.
Purpose of the Study:
- To investigate the molecular effects of isoflavone aglycones on uterine cells.
- To explore the role of isoflavones in regulating key uterine factors like LIF, TGF-beta, and glycodelin.
Main Methods:
- Utilized Ishikawa cells and primary human endometrial epithelial cells.
- Assayed protein secretion and expression using western blot and immunochemical staining.
- Investigated signaling pathways involving estrogen receptors, MEK1/2, p38 MAPK, and PKA.
Main Results:
- AglyMax, genistein, and equol modulated LIF and TGF-beta secretion in Ishikawa cells, dependent on estrogen receptor, MEK1/2, and p38 MAPK pathways.
- AglyMax and genistein increased cyclic AMP release and glycodelin expression, pathways involving MEK1/2 and PKA.
- AglyMax stimulated LIF, TGF-beta, and glycodelin in primary endometrial cells across menstrual phases.
Conclusions:
- Isoflavone aglycones can regulate uterine expression of estrogen-responsive genes.
- These effects involve modulation of LIF, TGF-beta, and glycodelin through specific signaling pathways.
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