Human endometrial cytodifferentiation by histone deacetylase inhibitors
Human endometrial cytodifferentiation by histone deacetylase inhibitors
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DOI：
10.1111/j.1749-0774.2005.00006.x
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发表时间：
2006-02
期刊：
影响因子：
4.3
通讯作者：
H. Uchida;T. Maruyama;T. Nagashima;M. Ono;H. Masuda;T. Arase;I. Sugiura;M. Onouchi;Takashi Kajitani;H. Asada;Y. Yoshimura
中科院分区：
文献类型：
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作者：
H. Uchida;T. Maruyama;T. Nagashima;M. Ono;H. Masuda;T. Arase;I. Sugiura;M. Onouchi;Takashi Kajitani;H. Asada;Y. Yoshimura
人子宫内膜在月经期间重复增殖、分化（蜕膜化）和组织分解。卵巢类固醇激素的适当分泌调节这些连续的子宫内膜重塑周期。对子宫内膜分化障碍，包括反复着床障碍，采用孕酮替代治疗，效果不明显。组蛋白可逆乙酰化在基因转录过程中起着关键作用，受组蛋白乙酰转移酶和组蛋白去乙酰化酶的调控。虽然，在用组蛋白脱乙酰酶抑制剂（HDACI）培养的细胞中，与未处理的对照细胞相比，仅约2%的表达基因的表达改变两倍或更多。许多先前的工作已经证明HDACI影响多种类型细胞中的细胞增殖/凋亡。迄今为止，几种HDACI作为抗癌药物处于I期或II期临床试验中。然而，还没有发现HDACI对人子宫内膜转分化有用的报道。最近，我们报道HDACI可诱导人子宫内膜间质细胞和上皮细胞表达分化标志蛋白，并引起形态学改变和功能性细胞分化。本文综述了HDACI对人子宫内膜细胞分化的影响，指出HDACI不仅可以作为抗癌药物，而且可以作为转分化试剂，基于一种新的策略。
Human uterine endometrium repeats proliferation, differentiation (decidualization) and tissue breakdown during the menstrual period. Appropriate secretion of ovarian steroid hormones regulates these sequential endometrial remodeling cycles. While progesterone replacement therapy is adopted for endometrial dysfunction of differentiation, including recurrent impairment of implantation, no obvious effective results are obtained. Histone reversible acetylation, regulated by histone acetyltransferases and histone deacetylases plays a pivotal role in gene transcription. Although, in cells cultured with histone deacetylase inhibitors (HDACI), the expression of only about 2% of expressed genes is changed twofold or more compared with untreated control cells. Numerous previous works have demonstrated that HDACI affect cell proliferation/apoptosis in a variety of types of cells. To date, several HDACI are in phase I or phase II clinical trials as anti-cancer drugs. However, no reports have been found that HDACI is useful for transdifferentiation in human endometrium. Recently, we reported that HDACI could induce the expression of differentiation marker proteins, morphological change and functional cytodifferentiation in both human endometrial stromal and epithelial cells. In this review, we summarize the effect of HDACI against the human endometrial cytodifferentiation, indicating the possibility that HDACI can be used not only as an anticancer drug, but also as a transdifferentiation reagent, based on a new strategy.