2011 Fiscal Year Final Research Report
SIRT1 as a therapeutic target of implantation failure
| Project/Area Number |
22791515
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIRAIKE Osamu 東京大学, 医学部附属病院, 助教 (20529060)
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| Project Period (FY) |
2010 – 2011
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| Keywords | SIRT1 / レスベラトロール / E-cadherin / 胚受容能 / 転写因子 |
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| Research Abstract |
Background : Sirtuin 1(SIRT1), originally found as a class III histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. We examined the role of SIRT1 in the regulation of uterine receptivity using Ishikawa and RL95-2 endometrial carcinoma cell lines.
Methodology/Principal Findings : Exogenous expression of SIRT1 significantly enhanced E-cadherin expression, while small interfering RNA-mediated depletion of endogenous SIRT1 resulted in a significant reduction of E-cadherin expression. A SIRT1 activator resveratrol elevated E-cadherin expression in a dose dependent manner, while SIRT1 repressors nicotinamide and sirtinol exhibited a dose dependent reduction of E-cadherin expression. We also showed that both forced expression of SIRT1 and activation of SIRT1 promote E-cadherin-driven reporter gene constructs, and SIRT1 is localized at E-cadherin promoter containing E-box elements in Ishikawa cells. Using an in vitro model of embryo implantation, we demonstrate that exogenous expression of SIRT1 and stimulation of SIRT1 activity resulted in the Ishikawa cell line becoming receptive to JAR cell spheroid attachment. Furthermore, resveratrol enhanced E-cadherin and Glycodelin protein expression at sites of intercellular contact, suggesting an additive role of resveratrol in promoting implantation.
Conclusions : The initial step of human reproduction depends on the capacity of an embryo to attach and implant into the endometrial wall, and these results revealed the novel mechanism that activation and increased expression of SIRT1 play an important role in uterine receptivity.
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Research Products
(12 results)
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[Journal Article] Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells : an implicative role of SIRT1 in the ovary2012
Author(s)
Morita Y, Wada-Hiraike O, Yano T, Shirane A, Hirano M, Hiraike H, Koyama S, Oishi H, Yoshino O, Miyamoto Y, Sone K, Oda K, Nakagawa S, Tsutsui K, Taketani Y
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Journal Title
Reprod Biol Endocrinol
Volume: 10
Pages: 10
Peer Reviewed
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[Journal Article] Multifunctional transcription factor TFII-I is an activator of BRCA1 function2011
Author(s)
Tanikawa M, Wada-Hiraike O, Nakagawa S, Shirane A, Hiraike H, Koyama S, Miyamoto Y, Sone K, Tsuruga T, Nagasaka K, Matsumoto Y, Ikeda Y, Shoji K, Oda K, Fukuhara H, Nakagawa K, Kato S, Yano T, Taketani Y
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Journal Title
Br J Cancer
Volume: 104
Pages: 1349-55
Peer Reviewed
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