Estrogen promotes the growth of decidual stromal cells in human early pregnancy
Estrogen promotes the growth of decidual stromal cells in human early pregnancy
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雌激素促进人类妊娠早期蜕膜基质细胞的生长。
DOI：
10.1093/molehr/gat034
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发表时间：
2013-10-01
影响因子：
4
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Shao, Jun;Li, Ming-Qing;Li, Da-Jin
白介素24(IL-24)是一种新的肿瘤抑制基因，在多种人类肿瘤细胞中具有抑制活性。本研究旨在阐明IL-24及其受体(IL-20R1、IL-20R2和IL-22R1)在人母胎界面蜕膜基质细胞(DSCs)中的生物学功能。采用四甲基偶氮唑盐比色法、四甲基偶氮唑蓝(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法和细胞凋亡率检测DSCs的体外行为。采用ELISA法、细胞内免疫印迹法和流式细胞术分别检测妊娠相关激素对IL-24的影响及IL-24对相应功能分子的影响。在此，我们发现DSCs表达IL-24及其受体，而IL-24明显抑制DSCs的活性并刺激其凋亡。相反，抗IL-24和IL-22R1中和抗体均能明显促进细胞生长，减少细胞凋亡。雌激素可显著降低IL-24的表达，但不影响IL-24的受体表达，这种作用可被雌激素受体β拮抗剂(ER-β)所阻断。IL-24显著抑制雌激素对DSCs活性、抗凋亡、抗凋亡基因Bcl2和增殖相关基因Ki 67的刺激作用。我们的研究表明，IL-24/IL-20R2/IL-22R1轴通过上调Bcl2和Ki67的表达参与雌激素/雌激素受体β信号对DSC生长的调控，提示雌激素通过下调IL-24在DSC生长中起重要作用。
Interleukin-24 (IL-24) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells. The present study aimed to elucidate the biological function of IL-24 and its receptors (IL-20R1, IL-20R2 and IL-22R1) in decidual stromal cells (DSCs) at human maternal-fetal interface. The DSCs behaviors in vitro were verified by viability (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptosis assay, respectively. Additionally, the effects of pregnancy-associated hormones on IL-24 and the effect of IL-24 on the correspondent functional molecules were investigated by ELISA, in-cell western and flow cytometry, respectively. Here we found that DSCs expressed IL-24 and its receptors, and IL-24 obviously suppressed the viability and stimulated the apoptosis in DSCs. On the contrary, both anti-IL-24 and IL-22R1 neutralizing antibodies markedly promoted growth and reduced the apoptosis. Estrogen but not progesterone could significantly decrease IL-24 but not its receptors, and these effects could be abolished by the antagonist of estrogen receptor beta (ERβ). IL-24 significantly restricted the stimulatory effect of estrogen on the viability, anti-apoptosis, anti-apoptosis gene Bcl-2 and proliferation relative gene Ki-67 in DSCs. Our study has demonstrated that IL-24/IL-20R2/IL-22R1 axis is involved in the regulation of estrogen/ERβ signaling on the growth of DSCs through up-regulating the expression of Bcl-2 and Ki67, which suggests that estrogen plays an important role in DSC growth of the early pregnancy through down-regulating IL-24.