Involvement of Histone Acetylation in Ovarian Steroid-induced Decidualization of Human Endometrial Stromal Cells

Sakai, Nozomi; Maruyama, Tetsuo; Sakurai, Rei; Masuda, H.; Yamamoto, Yurie; Shimizu, Aki; Kishi, Ikuko; Asada, Hironori; Yamagoe, Satoshi; Yoshimura, Yasunori

doi:10.1074/jbc.m211715200

Cited by 79 publications

(60 citation statements)

References 43 publications

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“…Histone deacetylase inhibitors (HDACIs), which induce hyperacetylation of chromatin, facilitate the transcription of several genes. In this manner, they stimulate decidualization of human endometrial stromal cells in vitro [45]. In addition, HDACIs, through up-regulation of glycodelin, an implantation-related protein, also stimulate differentiation and cell motility of the endometrial epithelial cell line, Ishikawa [46,47].…”

Section: Pr-associated Decidual Proteinsmentioning

confidence: 99%

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

2008

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Abstract. The human endometrium undergoes cyclical changes including proliferation, differentiation, tissue breakdown, and shedding (menstruation) throughout a woman's reproductive life. The postovulatory rise in ovarian progesterone induces profound remodeling and differentiation of the estradiol-primed endometrium. This change, termed decidualization, is crucial for embryo implantation and maintenance of the pregnancy. To date, activation and crosstalk of cAMP-and progesterone-mediated signaling pathways have emerged as key cellular events to drive integrated changes at both the transcriptome and the proteome levels. This results in the induction and maintenance of the decidual phenotype and function. Our recent series of studies highlights the critical role of SRC kinase activation (v-src sarcoma viral oncogene homolog) and STAT5 (signal transducer and activator of transcription 5) phosphorylation in decidualization. After separation of the functional layer of the differentiated endometrium that follows progesterone withdrawal, i.e., menstruation, the basal layer of the endometrium, under the influence of estradiol, regrows and initiates a unique form of angiogenesis and regenerates a new functional layer. The molecular and cellular mechanisms for this process remain elusive, mainly because of difficulties in reproducing menstrual tissue breakdown, shedding, and subsequent tissue regeneration in vitro. We have recently developed a "humanized" mouse model in which a functional human endometrium is reconstituted. It may be used as an in vivo experimental tool for the study of endometrial angiogenesis and regeneration. This model may also be used to identify and test new therapeutic strategies for endometriosis, endometrial cancer, implantation failure, and infertility related to endometrial dysfunction.

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Section: Pr-associated Decidual Proteinsmentioning

confidence: 99%

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

2008

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“…Human endometrial specimens were dissociated mechanically and enzymatically, filtrated, isolated by Ficoll gradient, and finally separated into endometrial stromal and glandular epithelial cell fractions as described previously (31,32), with certain modifications. In brief, endometrial tissue samples were cut into small pieces and digested with 0.2% (wt/vol) collagenase (Wako, Osaka, Japan) and 0.05% DNase I (GIBCO, Carlsbad, CA) in DMEM for 1.5 h at 37°C on a shaking rotor.…”

Section: Methodsmentioning

confidence: 99%

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice

Masuda

Maruyama²,

Hiratsu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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146

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Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/␥ c null immunodeficient mice. In addition to the endometrium-like structure, hormonedependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.animal model ͉ bioluminescence imaging ͉ endometriosis ͉ menstruation ͉ angiogenesis H uman endometrium lines the uterus and comprises luminal and glandular epithelial cells, stromal fibroblasts, vascular smooth muscle cells, endothelial cells, and immune competent cells. These cell components coordinately participate in the cyclical changes of human endometrium, including proliferation, differentiation, and tissue breakdown and shedding under the influence of estrogen and progesterone during the menstrual cycle. This unique system of cyclic tissue regeneration also depends on the cyclical growth and regression of the blood vessels that supply the endometrium (1). In addition, angiogenesis is deeply involved in the pathogenesis of endometriumderived disorders such as endometriosis (2). Endometriosis, one of the most common gynecological diseases, is characterized by the presence of functional endometrial-like tissue outside the uterine cavity. It is an estrogen-dependent disorder associated with substantial morbidity; however, the etiology and pathophysiology are not well elucidated (3). To study the physiology of normal endometrium and the pathogenesis of endometriosis, a variety of in vivo models using small animals has been developed by using the transplantation of autologous or heterologous endometrial cells/tissues or endometriotic tissues (4).In the present study, taking advantage of newly de...

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“…Cell lines were treated with varying doses of 5-aza-CdR (Sigma, St. Louis, MO), a specific inhibitor of DNA methyltransferase, ranging from 2 to 10 μM for various times (18).…”

Section: Reverse-transcription Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells

Yashiro

Yasuda²,

Nishii³

et al. 2009

Int J Oncol

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Abstract. ERas is a recently identified oncogene that supports the tumorigenic growth of embryonic stem cells, it is constitutively active in the absence of mutation. ERas oncogene is expressed only in viviparity phase cells, but not in somatic cells because of epigenetic transcriptional silencing in the somatic phase. The aim of this study was to clarify the ERas expression and its epigenetic regulation in gastric cancer of somatic phase. Fifteen gastric cancer cell lines were used. ERas mRNA expression and its epigenetic regulation were examined by reverse transcription-polymerase chain reaction and bisulfite sequencing analysis. To identify a subset of cancer stem cells, termed 'side population' (SP) cells, flow cytometry analysis was performed. ERas is expressed in 8 of the 15 gastric cancer cell lines, but is silenced in the remaining 7 cancer cell lines and normal cell lines. Six of 7 cancer cell lines without ERas expression had promoter methylation, which correlated with silencing of ERas expression. ERas expression is re-activated following treatment with the DNA methyltransferase inhibitor 5-azaCdR. The percentage of SP fraction of ERas-positive gastric cancer cells was significantly (p=0.024) higher (3.4±1.8%), in comparison to that of ERas-negative cells (1.6±0.4%). These findings suggested that the activating ERas oncogene might be associated with tumorigenic growth of somatic cells, and might be a putative molecule responsible for cancer stem celllike characteristics in gastric cancer. Loss of methylation in the promoter of ERas might be one of mechanisms responsible for the re-expression of an embryonic oncogene in gastric cancer.

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Involvement of Histone Acetylation in Ovarian Steroid-induced Decidualization of Human Endometrial Stromal Cells

Cited by 79 publications

References 43 publications

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice

Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells

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Involvement of Histone Acetylation in Ovarian Steroid-induced Decidualization of Human Endometrial Stromal Cells

Cited by 79 publications

References 43 publications

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

Molecular and Cellular Mechanisms for Differentiation and Regeneration of the Uterine Endometrium

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ c null immunodeficient mice

Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells

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Product

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Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice