Guo Chuan-Hui, Yue Zhan-Peng, Bai Zhi-Kun, Li Dang-Dang, Yang Zhan-Qing, Guo Bin
College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Cell Tissue Res. 2016 Nov;366(2):393-401. doi: 10.1007/s00441-016-2412-z. Epub 2016 May 5.
Although Runx2 is involved in the regulation of cellular differentiation, its physiological roles in the differentiation of uterine stromal cells during decidualization still remain unknown. The aim of this study was to examine the expression, regulation and function of Runx2 in mouse uterus during decidualization. The results showed that Runx2 was highly expressed in the decidua and oil-induced decidualized cells. In the uterine stromal cells, recombinant human Runx2 (rRunx2) could induce the expression of Prl8a2 and Prl3c1 which are two well-known differentiation markers for decidualization, while inhibition of Runx2 with specific siRNA reduced their expression. Further study found that rRunx2 could improve the expression of Prl8a2 and Prl3c1 in the C/EBPβ siRNA-transfected stromal cells. In the stromal cells, cAMP analogue 8-Br-cAMP could induce the expression of Runx2. Moreover, the induction was blocked by PKA inhibitor H89. Simultaneously, attenuation of C/EBPβ with siRNA could also reduce the cAMP-induced Runx2 expression. Furthermore, siRNA-mediated silencing of Runx2 expression alleviated the effects of cAMP on the differentiation of stromal cells. Runx2 might act downstream of C/EBPβ to regulate the expression of Cox-2, Vegf and Mmp9 in the uterine stromal cells. Collectively, Runx2 may play an important role during mouse decidualization.
尽管Runx2参与细胞分化的调控，但其在蜕膜化过程中子宫基质细胞分化中的生理作用仍不清楚。本研究的目的是检测Runx2在小鼠子宫蜕膜化过程中的表达、调控及功能。结果显示，Runx2在蜕膜和油诱导的蜕膜化细胞中高表达。在子宫基质细胞中，重组人Runx2（rRunx2）可诱导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Runx2则会降低它们的表达。进一步研究发现，rRunx2可提高C/EBPβ siRNA转染的基质细胞中Prl8a2和Prl3c1的表达。在基质细胞中，cAMP类似物8-Br-cAMP可诱导Runx2的表达。此外，PKA抑制剂H89可阻断这种诱导作用。同时，用siRNA减弱C/EBPβ也可降低cAMP诱导的Runx2表达。此外，siRNA介导的Runx2表达沉默可减轻cAMP对基质细胞分化的影响。Runx2可能在C/EBPβ的下游发挥作用，以调节子宫基质细胞中Cox-2、Vegf和Mmp9的表达。总之，Runx2可能在小鼠蜕膜化过程中发挥重要作用。
