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雌激素调节脯氨酸丰富酸性蛋白 1 被 I 类组蛋白去乙酰化酶抑制,并在植入前小鼠子宫中发挥作用。

Estradiol-regulated proline-rich acid protein 1 is repressed by class I histone deacetylase and functions in peri-implantation mouse uterus.

机构信息

State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Rd., Chaoyang, Beijing 100101, China.

出版信息

Mol Cell Endocrinol. 2011 Jan 1;331(1):23-33. doi: 10.1016/j.mce.2010.06.003. Epub 2010 Jun 12.

DOI:10.1016/j.mce.2010.06.003
PMID:20547205
Abstract

Secretory protein proline-rich acid protein 1 (PRAP1) is abundantly expressed in late pregnant uterus. However, regulation and function of PRAP1 in pregnant uterus is still elusive. We firstly reported differential expression of PRAP1 in peri-implantation uteri and its localization in endometrial epithelia. Expression of PRAP1 in uterus was induced by 17β-estradiol and its expression showed a negative correlation with that of class Ihistone deacetylases (HDACs) in isolated endometrial epithelia. PRAP1 was increased by HDACs inhibitor sodium butyrate treatment, while decreased significantly by estrogen receptor inhibitor ICI182,780 via up-regulating class IHDACs. Number of implanted embryos was decreased in mice immunized with pCR3.1-PRAP1 or injected with rabbit anti-PRAP1 antibody. DNA immunization or antibody injection could affect apoptosis and expression of cytokines (IL-4, IFN-γ). In conclusion, both 17β-estradiol and class IHDACs are involved in modulating PRAP1 expression in peri-implantation uteri. Preliminary functional research indicates that neutralizing PRAP1 protein causes reduction of implanted embryos.

摘要

富含脯氨酸酸性蛋白 1(PRAP1)是一种分泌蛋白,在妊娠晚期的子宫中大量表达。然而,PRAP1 在妊娠子宫中的调控和功能仍不清楚。我们首次报道了 PRAP1 在着床前后子宫中的差异表达及其在内膜上皮细胞中的定位。17β-雌二醇诱导了 PRAP1 在子宫中的表达,并且其表达与分离的子宫内膜上皮细胞中 I 类组蛋白去乙酰化酶(HDACs)的表达呈负相关。HDACs 抑制剂丁酸钠处理可增加 PRAP1 的表达,而雌激素受体抑制剂 ICI182,780 通过上调 I 类 HDACs 使 PRAP1 表达显著降低。用 pCR3.1-PRAP1 免疫或注射兔抗 PRAP1 抗体的小鼠,胚胎着床数量减少。DNA 免疫或抗体注射可影响细胞凋亡和细胞因子(IL-4、IFN-γ)的表达。总之,17β-雌二醇和 I 类 HDACs 都参与调节着床前后子宫中 PRAP1 的表达。初步功能研究表明,中和 PRAP1 蛋白会导致着床胚胎减少。

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