Center for Reproductive MedicineRen Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai, China.
J Mol Endocrinol. 2018 Feb;60(2):133-143. doi: 10.1530/JME-17-0180. Epub 2017 Dec 22.
Preeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria after 20 weeks of gestation, affecting 5-7% of pregnancies worldwide. So far, the etiology of PE remains poorly understood. Abnormal decidualization is thought to contribute to the development of PE. SP1 belongs to the Sp/KLF superfamily and can recruit P300 to regulate the transcription of several genes. SP1 is also very important for decidualization as it enhances the expression of tissue factor. In this study, we investigated the expression of SP1 and P300 in deciduae and their relationship with PE. A total of 42 decidua samples were collected, of which 21 were from normal pregnant (NP) and 21 from severe PE. SP1 and P300 expression in deciduae and the levels of SP1 and P300 in cultured human endometrial stromal cells (hESCs) and primary hESCs during decidualization were determined. To further investigate the role of SP1 and P300 in human decidualization, RNA interference was used to silence SP1 and P300 in hESCs and primary hESCs. The following results were obtained. We found that the expressions of SP1 and P300 were reduced in decidual tissues with PE compared to those from NP. In the model of induction of decidualization, we found an increase in both and levels. Silencing of and resulted in abnormal decidualization and a significant reduction of decidualization markers such as insulin-like growth factor-binding protein1 and prolactin. Furthermore, the expression of vascular endothelial growth factor was also decreased upon and silencing. Similar results were observed in primary hESCs. Our results suggest that SP1 and P300 play an important role during decidualization. Dysfunction of SP1 and P300 leads to impaired decidualization and might contribute to PE.
子痫前期 (PE) 是一种妊娠诱发的疾病，其特征是在妊娠 20 周后出现高血压和蛋白尿，影响全球 5-7%的妊娠。迄今为止，PE 的病因仍知之甚少。异常的蜕膜化被认为有助于 PE 的发展。SP1 属于 Sp/KLF 超家族，可募集 P300 来调节几个基因的转录。SP1 对蜕膜化也非常重要，因为它增强了组织因子的表达。在这项研究中，我们研究了 SP1 和 P300 在蜕膜中的表达及其与 PE 的关系。共收集了 42 个蜕膜样本，其中 21 个来自正常妊娠（NP），21 个来自严重 PE。检测了蜕膜中 SP1 和 P300 的表达，以及培养的人子宫内膜基质细胞（hESC）和蜕膜化过程中初级 hESC 中 SP1 和 P300 的水平。为了进一步研究 SP1 和 P300 在人蜕膜化中的作用，我们使用 RNA 干扰沉默了 hESC 和初级 hESC 中的 SP1 和 P300。结果如下。我们发现与 NP 相比，PE 蜕膜组织中 SP1 和 P300 的表达减少。在诱导蜕膜化的模型中，我们发现两者的水平都增加了。沉默 和 导致蜕膜化异常，蜕膜化标志物如胰岛素样生长因子结合蛋白 1 和催乳素的水平显著降低。此外，沉默 和 后血管内皮生长因子的表达也降低。在初级 hESC 中也观察到类似的结果。我们的结果表明，SP1 和 P300 在蜕膜化过程中发挥重要作用。SP1 和 P300 的功能障碍导致蜕膜化受损，可能导致 PE。
