We previously reported that the transcription factor Wilms tumor 1 (WT1) regulates the expression of insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) during decidualization of human endometrial stromal cells (ESCs). However, other roles of WT1 in decidualization remain to be fully clarified. Here, we investigated how WT1 regulates the physiological functions of human ESCs during decidualization. We incubated ESCs isolated from proliferative-phase endometrium with cAMP to induce decidualization, knocked down WT1 with siRNA, and generated three types of treatments (non-treated cells, cAMP-treated cells, and cAMP-treated + WT1-knockdown cells). To identify WT1-regulated genes, we used gene microarrays and compared the transcriptome data obtained among these three treatments. We observed that WT1 up-regulates 121 genes during decidualization, including several genes involved in lipid transport. The WT1 knockdown inhibited lipid accumulation (LA) in the cAMP-induced ESCs. To examine the mechanisms by which WT1 regulates LA, we focused on very low-density lipoprotein receptor (VLDLR), which is involved in lipoprotein uptake. We found that cAMP up-regulates VLDLR and that the WT1 knockdown inhibits it. Results of ChIP assays revealed that cAMP increases the recruitment of WT1 to the promoter region of the VLDLR gene, indicating that WT1 regulates VLDLR expression. Moreover, VLDLR knockdown inhibited cAMP-induced LA, and VLDLR overexpression reverted the suppression of LA caused by the WT1 knockdown. Taken together, our results indicate that WT1 enhances lipid storage by up-regulating VLDLR expression in human ESCs during decidualization.

中文翻译：

---

Wilms肿瘤1蜕膜化过程中调节人类子宫内膜基质细胞的脂质蓄积。

我们先前曾报道，在子宫内膜间质细胞（ESCs）蜕膜化过程中，转录因子Wilms肿瘤1（WT1）调节胰岛素样生长因子结合蛋白1（IGFBP-1）和催乳素（PRL）的表达。但是，WT1在蜕皮化中的其他作用仍有待充分阐明。在这里，我们调查了WT1在蜕膜化过程中如何调节人类ESC的生理功能。我们用cAMP培养从增殖期子宫内膜分离的ESC，以诱导蜕膜形成，用siRNA敲低WT1，并产生三种类型的处理（未处理的细胞，cAMP处理的细胞和cAMP处理的+ WT1敲除细胞）。为了鉴定WT1调节的基因，我们使用基因芯片，比较了这三种处理中获得的转录组数据。我们观察到WT1在蜕膜化过程中上调了121个基因，包括参与脂质转运的几个基因。WT1组合式抑制cAMP诱导的ESC中的脂质蓄积（LA）。为了检查WT1调节LA的机制，我们集中在涉及脂蛋白摄取的极低密度脂蛋白受体（VLDLR）上。我们发现cAMP上调了VLDLR，而WT1的抑制则抑制了它。ChIP分析的结果表明，cAMP可增加WT1向VLDLR基因的启动子区域的募集，表明WT1调节VLDLR表达。此外，VLDLR抑制可抑制cAMP诱导的LA，而VLDLR过表达可逆转WT1抑制对LA的抑制作用。在一起