Lactogenic hormone stimulation and epigenetic control of L-amino acid oxidase expression in lactating mammary glands
Lactogenic hormone stimulation and epigenetic control of L-amino acid oxidase expression in lactating mammary glands
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DOI：
10.1002/jcp.25000
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发表时间：
2015-11-01
影响因子：
5.6
通讯作者：
Nagaoka, Kentaro
中科院分区：
文献类型：
--
作者：
Fujii, Kazuki;Zhang, Haolin;Nagaoka, Kentaro
l -氨基酸氧化酶（LAO）是一种经典的黄酮类蛋白，通过产生过氧化氢来显示抗菌活性。LAO存在于唾液腺、胸腺、脾脏、小肠和睾丸等许多组织中。特别是，LAO在小鼠乳中高表达，在乳腺先天免疫中起重要作用。然而，在哺乳乳腺中，LAO表达的时空调控机制尚不清楚。在本研究中，我们展示了乳源激素和表观遗传控制对LAO基因表达的贡献。在单层乳腺上皮细胞中，乳原激素、地塞米松、胰岛素和催乳素混合处理未诱导LAO mRNA的表达及其启动子活性，但乳蛋白-酪蛋白之一的表达受到刺激。然而，当细胞在三维培养中被产乳激素处理时，观察到LAO表达增加。染色质免疫沉淀分析结果显示，哺乳时组蛋白H3K18乙酰化升高，组蛋白H3K27三甲基化降低，这与LAO高表达期有关。此外，组蛋白甲基化抑制剂（DZNep）和组蛋白去乙酰化抑制剂（Trichostatine A）处理可诱导乳腺细胞单层中LAO的表达。综上所述，这是第一次在细胞培养中诱导LAO表达，而促乳激素的刺激和组蛋白修饰的改变是显示泌乳乳腺中LAO高表达的有希望的信号。j .细胞。中国生物医学工程学报，2015,31(2):555 - 562。(c) 2015 Wiley期刊公司
L-amino acid oxidase (LAO), a classic flavoprotein, shows antibacterial activity by producing hydrogen peroxide. LAO exists in many tissues such as salivary gland, thymus, spleen, small intestine and testis. In particular, LAO was highly expressed in mice milk and plays an important factor in innate immunity of mammary glands. However, the mechanism which LAO expression is regulated spatially and temporally in lactating mammary glands has been unclear. In this study, we showed the contribution of lactogenic hormone and epigenetic control on LAO gene expression. In monolayer of mammary epithelial cells, treatment of lactogenic hormone mixture, dexamethasone, insulin and prolactin, did not induce LAO mRNA expression and its promoter activity, even though one of milk protein -casein expression was stimulated. However, increase of LAO expression was observed when the cells were treated with lactogenic hormones in a 3-dimensional culture. The results of chromatin immunoprecipitation analysis revealed that histone H3K18 acetylation increased and histone H3K27 tri-methylation decreased with lactation, which is associated with a period of high LAO expression. Moreover, the treatment of histone methylation inhibitor (DZNep) as well as histone deacetylation inhibitor (Trichostatine A) induced LAO expression in monolayer of mammary cells. Taken together, this is the first demonstration showing that LAO expression is induced in cell culture, and stimulation of lactogenic hormone and change of histone modification are promising signals to show highly expression of LAO in lactating mammary glands. J. Cell. Physiol. 9999: 2755-2762, 2015. (c) 2015 Wiley Periodicals, Inc.