Reproductive Medicine Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China.
Biochem Biophys Res Commun. 2013 Mar 29;433(1):11-7. doi: 10.1016/j.bbrc.2013.02.078. Epub 2013 Feb 28.
Members of the KLFs family of transcription factors play roles in maternal endometrium development during embryo implantation. However, the specific role of KLF12 in endometrium development has not yet been described. In this study, we showed that KLF12 expression in human endometrial stromal cells (HESCs) was significantly decreased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). The adenovirus-mediated overexpression of KLF12 in HESCs significantly repressed the expression and secretion of decidualization biomarker genes and their products decidual prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) induced by 8-Br-cAMP and MPA. Moreover, CHIP and luciferase reporter assays demonstrated that KLF12 bound to a CAGTGGG element within the decidual prolactin promoter and decreased decidual PRL promoter (dPRL/-2000Luc) activation in a sequence-specific manner. Taken together, these findings suggest KLF12 is a negative regulator of human endometrial stromal cell decidualization.
KLFs 转录因子家族成员在胚胎植入过程中母体内膜的发育中发挥作用。然而，KLF12 在子宫内膜发育中的具体作用尚未被描述。在这项研究中，我们表明，在人子宫内膜基质细胞（HESCs）中，8-Br-cAMP 和醋酸甲羟孕酮（MPA）刺激的蜕膜化后，KLF12 的表达显著降低。腺病毒介导的 KLF12 在 HESCs 中的过表达显著抑制了由 8-Br-cAMP 和 MPA 诱导的蜕膜化生物标志物基因及其产物蜕膜催乳素（PRL）和胰岛素样生长因子结合蛋白-1（IGFBP-1）的表达和分泌。此外，CHIP 和荧光素酶报告基因分析表明，KLF12 与催乳素启动子内的 CAGTGGG 元件结合，并以序列特异性方式降低催乳素启动子（dPRL/-2000Luc）的激活。总之，这些发现表明 KLF12 是人类子宫内膜基质细胞蜕膜化的负调控因子。
