Functional analysis of glycodelin induced by HDACI in endometrial glandular epithelium.

HDACI 在子宫内膜腺上皮中诱导的甘氨肽的功能分析。

• 批准号: 16591683
• 负责人: UCHIDA Hiroshi
• 金额: $ 2.3万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591683/
• 关键词: human endometrium; histone deacetylase inhibitor; differentiation; migration; glycodelin; 細胞浸潤; glycodelin

Human uterine endometrium repeats proliferation, differentiation (decidualization) and tissue breakdown during the menstrual period. Histone reversible acetylation, regulated by histone acetylase and deacetylase, govern gene transcription. To develop new strategy of treatment for impairment of implantation, we analyze the possibility of histone deacetylase inhibitors (HDACI) as a differentiation inducer of human endometrium, instead of ovarian steroid hormones.We analyzed the effect of ovarian steroid hormones or HDACI onto Ishikawa cells (human adenocarcinoma cell line), which is used as a model of human endometrial glandular epithelium. In a similar way to ovarian steroid hormones, HDACI affected the following function in Ishikawa cells.1)HDACI induced the both mRNA and protein expression of glycodelin, which is highly expressed in differentiated (luteal-phase) endometrial gland, via glycodelin promoter region.2)Flattened and wide-spread morphological changes of cells were shown by HDACI.3)HDACI enhanced the production of glycogen.4)HDACI up-regulated single cell motility, analyzed with trans-well cell migration assay.5)HDACI enhanced collective cell motility, tested with wound healing assay.6)Glycodelin permanent expression clones showed accelerated single and collective cell migration.7)Glycodelin gene silencing by siRNA abolished the effect by HDACI, mentioned above.Taken together, HDACI have a potential to induce both differentiation and migration of endometrial cells through up-regulation of glycodelin, providing a clue for a possible therapeutic strategy to modulate endometrial function by targeting glycodelin.

人子宫内膜重复增殖，分化（去个体化）和组织破坏在月经期间。组蛋白可逆乙酰化受组蛋白乙酰化酶和去乙酰化酶调控，控制基因转录。为了开发新的治疗植入障碍的策略，我们分析了组蛋白去乙酰化酶抑制剂（HDACI）替代卵巢类固醇激素作为人子宫内膜分化诱导剂的可能性。我们分析了卵巢类固醇激素或HDACI对石川细胞（人腺癌细胞系）的影响，石川细胞被用作人子宫内膜腺上皮的模型。与卵巢类固醇激素类似，HDACI影响石川细胞的以下功能。1)HDACI通过糖苷启动子区诱导分化（黄体期）子宫内膜高表达的糖苷mRNA和蛋白表达。2) HDACI可使细胞呈扁平状、大范围形态学改变。3)HDACI可促进糖原的生成。4)HDACI上调单细胞运动，跨孔细胞迁移实验分析。5)HDACI增强了细胞的集体运动，用伤口愈合实验检测。(6)糖苷永久表达克隆单细胞和集体细胞迁移速度加快。7) siRNA沉默糖苷基因可消除上述HDACI的作用。综上所述，HDACI有可能通过上调糖苷介导子宫内膜细胞的分化和迁移，为靶向糖苷调节子宫内膜功能的治疗策略提供了线索。

项目成果

Follicle stimulating hormone secreting pituitary microadenoma with fluctuating levels of ovarian hyperstimulation

• DOI: 10.1097/01.aog.0000141554.50747.16
• 发表时间: 2005-05-01
• 期刊: OBSTETRICS AND GYNECOLOGY
• 影响因子: 7.2
• 作者: Maruyama, T;Masuda, H;Yoshimura, Y
• 通讯作者: Yoshimura, Y

Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin

• DOI: 10.1210/en.2005-0359
• 发表时间: 2005-12-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Uchida, H;Maruyama, T;Yoshimura, Y
• 通讯作者: Yoshimura, Y

Histone acetylation in reproductive organs: significance of histone deacetylase inhibitors in gene transcription. (Review)

生殖器官中的组蛋白乙酰化：组蛋白脱乙酰酶抑制剂在基因转录中的重要性。

• 发表时间: 2005
• 期刊: Reprod Med Biol 4(2)
• 作者: Uchida H;Maruyama T;Arase T;Ono M;Nagashima T;Masuda H;Asada H;Yoshimura Y
• 通讯作者: Yoshimura Y

Histone acetylation in reproductive organs Significance of histone deacetylase inhibitors in gene transcription

生殖器官中的组蛋白乙酰化 组蛋白脱乙酰酶抑制剂在基因转录中的意义

• 发表时间: 2005
• 期刊: Reprod Med Biol 4
• 作者: Uchida H;Maruyama T;Arase T;Ono M;Nagashima T;Masuda H;A sada H;Yoshimura Y
• 通讯作者: Yoshimura Y

Human endometrial cytodifferentiation by histone deacetylase inhibitors

• DOI: 10.1111/j.1749-0774.2005.00006.x
• 发表时间: 2006-02
• 期刊: Human Cell
• 影响因子: 4.3
• 作者: H. Uchida;T. Maruyama;T. Nagashima;M. Ono;H. Masuda;T. Arase;I. Sugiura;M. Onouchi;Takashi Kajitani;H. Asada;Y. Yoshimura