Hmgn5 functions downstream of Hoxa10 to regulate uterine decidualization in mice
Hmgn5 functions downstream of Hoxa10 to regulate uterine decidualization in mice
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Hmgn5 在 Hoxa10 下游发挥作用，调节小鼠子宫蜕膜化
DOI：
10.1080/15384101.2016.1220459
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发表时间：
2016-01-01
期刊：
影响因子：
4.3
通讯作者：
Guo, Bin
中科院分区：
文献类型：
--
作者：
Li, Dang-Dang;Zhao, Shu-Yi;Guo, Bin
Hmgn 5参与细胞增殖和分化的调控，但其在蜕膜化过程中的生理功能尚不清楚。我们发现Hmgn 5在蜕膜细胞中高度表达。通过特异性siRNA沉默Hmgn 5表达降低了子宫基质细胞的增殖以及在雌激素和孕激素存在或不存在的情况下Ccnd 3和Cdk 4的表达，而Hmgn 5的过表达表现出相反的效果。同时，Hmgn 5可能诱导Prl 8a 2和Prl 3c 1的表达，这是两个众所周知的蜕膜化分化标志物。在子宫基质细胞中，cAMP类似物8-Br-cAMP和孕酮可上调Hmgn 5的表达，但H89和RU 486分别抑制了这种上调作用。Hmgn 5表达减弱可阻断子宫间质细胞对cAMP和孕酮的反应性分化。进一步的研究发现cAMP和孕酮对Hmgn 5表达的调节是由Hoxa 10介导的。在体外蜕膜化过程中，Hmgn 5的敲低可以消除Hoxa 10诱导的Prl 8a 2和Prl 3c 1的上调，而Hmgn 5的过表达则逆转了Hoxa 10 siRNA对Prl 8a 2和Prl 3c 1表达的抑制作用。在蜕膜化的基质细胞中，Hmgn 5可能在Hoxa 10的下游调控考克斯-2、VEGF和Mmp 2的表达。总之，Hmgn 5可能在小鼠蜕膜化过程中发挥重要作用。
ABSTRACT Although Hmgn5 is involved in the regulation of cellular proliferation and differentiation, its physiological function during decidualization is still unknown. Here we showed that Hmgn5 was highly expressed in the decidual cells. Silencing of Hmgn5 expression by specific siRNA reduced the proliferation of uterine stromal cells and expression of Ccnd3 and Cdk4 in the absence or presence of estrogen and progesterone, whereas overexpression of Hmgn5 exhibited the opposite effects. Simultaneously, Hmgn5 might induce the expression of Prl8a2 and Prl3c1 which were 2 well-known differentiation markers for decidualization. In the uterine stromal cells, cAMP analog 8-Br-cAMP and progesterone could up-regulate the expression of Hmgn5, but the up-regulation was impeded by H89 and RU486, respectively. Attenuation of Hmgn5 expression could block the differentiation of uterine stromal cells in response to cAMP and progesterone. Further studies found that regulation of cAMP and progesterone on Hmgn5 expression was mediated by Hoxa10. During in vitro decidualization, knockdown of Hmgn5 could abrogate Hoxa10-induced upregulation of Prl8a2 and Prl3c1, while overexpression of Hmgn5 reversed the inhibitory effects of Hoxa10 siRNA on the expression of Prl8a2 and Prl3c1. In the stromal cells undergoing decidualization, Hmgn5 might act downstream of Hoxa10 to regulate the expression of Cox-2, Vegf and Mmp2. Collectively, Hmgn5 may play an important role during mouse decidualization.