Li Dang-Dang, Yang Zhan-Qing, Guo Chuan-Hui, Yue Liang, Duan Cui-Cui, Cao Hang, Guo Bin, Yue Zhan-Peng
a College of Veterinary Medicine; Jilin University ; Changchun , China.
b College of Clinical Medicine; Jilin University ; Changchun , China.
Cell Cycle. 2015;14(21):3461-74. doi: 10.1080/15384101.2015.1093704.
Although Hmgn1 is involved in the regulation of gene expression and cellular differentiation, its physiological roles on the differentiation of uterine stromal cells during decidualization still remain unknown. Here we showed that Hmgn1 mRNA was highly expressed in the decidua on days 6-8 of pregnancy. Simultaneously, increased expression of Hmgn1 was also observed in the artificial and in vitro induced decidualization models. Hmgn1 induced the proliferation of uterine stromal cells and expression of Ccna1, Ccnb1, Ccnb2 and Cdk1 in the absence of estrogen and progesterone. Overexpression of Hmgn1 could enhance the expression of Prl8a2 and Prl3c1 which were 2 well-known differentiation markers for decidualization, whereas inhibition of Hmgn1 with specific siRNA could reduce their expression. Further studies found that Hmgn1 could mediate the effects of C/EBPβ on the expression of Prl8a2 and Prl3c1 during in vitro decidualization. In the uterine stromal cells, cAMP analog 8-Br-cAMP could stimulate the expression of Hmgn1 via C/EBPβ. Moreover, siRNA-mediated down-regulation of Hmgn1 could attenuate the effects of cAMP on the differentiation of uterine stromal cells. During in vitro decidualization, Hmgn1 might act downstream of C/EBPβ to regulate the expression of Cox-2, mPGES-1 and Vegf. Progesterone could up-regulate the expression of Hmgn1 in the ovariectomized mouse uterus, uterine epithelial cells and stromal cells. Knockdown of C/EBPβ with siRNA alleviated the up-regulation of progesterone on Hmgn1 expression. Collectively, Hmgn1 may play an important role during mouse decidualization.
尽管Hmgn1参与基因表达调控和细胞分化，但其在蜕膜化过程中对子宫基质细胞分化的生理作用仍不清楚。在此我们发现，Hmgn1 mRNA在妊娠第6 - 8天的蜕膜中高表达。同时，在人工和体外诱导的蜕膜化模型中也观察到Hmgn1表达增加。在缺乏雌激素和孕激素的情况下，Hmgn1可诱导子宫基质细胞增殖以及Ccna1、Ccnb1、Ccnb2和Cdk1的表达。Hmgn1的过表达可增强Prl8a2和Prl3c1的表达，这两种蛋白是蜕膜化的两个著名分化标志物，而用特异性siRNA抑制Hmgn1可降低它们的表达。进一步研究发现，在体外蜕膜化过程中，Hmgn1可介导C/EBPβ对Prl8a2和Prl3c1表达的影响。在子宫基质细胞中，cAMP类似物8 - Br - cAMP可通过C/EBPβ刺激Hmgn1的表达。此外，siRNA介导的Hmgn1下调可减弱cAMP对子宫基质细胞分化的影响。在体外蜕膜化过程中，Hmgn1可能在C/EBPβ下游发挥作用，调节Cox - 2、mPGES - 1和Vegf的表达。孕激素可上调去卵巢小鼠子宫、子宫上皮细胞和基质细胞中Hmgn1的表达。用siRNA敲低C/EBPβ可减轻孕激素对Hmgn1表达的上调作用。总体而言，Hmgn1可能在小鼠蜕膜化过程中发挥重要作用。
