Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium.
Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium.
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DOI：
10.1186/s12958-022-00903-8
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发表时间：
2022-02-02
期刊：
影响因子：
--
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Zhu Q;Yao S;Dong Y;Liu D;Wang H;Jiang P;Dai C;Lv H;Cao C;Zhou Z;Wang L;Gou W;Zhang X;Zhao G;Hu Y
薄子宫内膜（TE）是生殖医学中一个具有挑战性的临床问题，其特点是子宫内膜厚度不足、对雌激素反应差且目前尚无有效的治疗方法。目前，薄型子宫内膜的确切发病机制仍有待阐明。我们的目的是通过比较 TE 与匹配对照之间增殖晚期子宫内膜的转录组图谱来探讨 TE 的相关分子机制。我们首次对 7 个 TE 和 7 个匹配对照的增殖晚期子宫内膜组织进行了批量 RNA 测序（RNA 测序）。进行差异基因表达分析、基因本体富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。免疫组织化学用于子宫内膜中的分子表达和定位。分离培养人子宫内膜基质细胞（HESC）以验证hub基因的功能。对子宫内膜 RNA-seq 数据的综合数据挖掘显示，大多数与细胞分裂和细胞周期相关的基因均受到显着抑制，而炎症激活、免疫反应和活性氧相关基因在 TE 中上调。 PBK被认为是PPIs网络的枢纽，其在TE患者子宫内膜中的表达水平降低了2.43倍，特别是在基质细胞中降低，与Ki67的表达降低相平行。体外实验表明，PBK的缺失使HESCs的增殖能力降低50%，并使HESCs的凋亡增加1倍，同时PBK的表达受到氧化应激（减少76.2%）、缺氧（减少51.9%）和炎症因子（减少约50%）的抑制。这些结果表明，PBK 表达不足与 TE 子宫内膜厚度较差有关。增殖后期的子宫内膜转录组显示，子宫内膜薄的女性的细胞增殖受到抑制，人子宫内膜基质细胞 (HESC) 中 PBK 的表达降低，炎症和活性氧是造成这种情况的原因。在线版本包含可在 10.1186/s12958-022-00903-8 获取的补充材料。
Thin endometrium (TE) is a challenging clinical issue in the reproductive medicine characterized by inadequate endometrial thickness, poor response to estrogen and no effective treatments currently. At present, the precise pathogenesis of thin endometria remains to be elucidated. We aimed to explore the related molecular mechanism of TE by comparing the transcriptome profiles of late-proliferative phase endometria between TE and matched controls. We performed a bulk RNA-Seq (RNA-sequencing) of endometrial tissues in the late-proliferative phase in 7 TE and 7 matched controls for the first time. Differential gene expression analysis, gene ontology enrichment analysis and protein-protein interactions (PPIs) network analysis were performed. Immunohistochemistry was used for molecular expression and localization in endometria. Human endometrial stromal cells (HESCs) were isolated and cultured for verifying the functions of hub gene. Integrative data mining of our RNA-seq data in endometria revealed that most genes related to cell division and cell cycle were significantly inhibited, while inflammation activation, immune response and reactive oxygen species associated genes were upregulated in TE. PBK was identified as a hub of PPIs network, and its expression level was decreased by 2.43-fold in endometria of TE patients, particularly reduced in the stromal cells, which was paralleled by the decreased expression of Ki67. In vitro experiments showed that the depletion of PBK reduced the proliferation of HESCs by 50% and increased the apoptosis of HESCs by 1 time, meanwhile PBK expression was inhibited by oxidative stress (reduced by 76.2%), hypoxia (reduced by 51.9%) and inflammatory factors (reduced by approximately 50%). These results suggested that the insufficient expression of PBK was involved in the poor endometrial thickness in TE. The endometrial transcriptome in late-proliferative phase showed suppressed cell proliferation in women with thin endometria and decreased expression of PBK in human endometrial stromal cells (HESCs), to which inflammation and reactive oxygen species contributed. The online version contains supplementary material available at 10.1186/s12958-022-00903-8.
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