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Abstract：
Recurrent spontaneous abortion (RSA) is a serious condition that adversely affects women\'s health. Differentially expressed proteins (DEPs) in plasma of patients experiencing RSA is helpful to find new therapeutic targets and identified with mass spectrometry. In 57 DEPs, 21 were upregulated and 36 were downregulated in RSA. Gene ontology analyses indicated that identified DEPs were associated with cell proliferation, including significantly downregulated insulin-like growth factor binding protein 2 (IGFBP2). Immunohistochemical result using clinical decidual tissues also showed that IGFBP2 expression was significantly decreased in RSA trophoblasts. Cell proliferation assay indicated that IGFBP2 treatment increased the proliferation and mRNA expressions of PCNA and Ki67 in trophoblast cells. Transcriptome sequencing experiments and Kyoto Encyclopedia of Genes and Genomes analyses revealed that gene expression for components in PI3K-Akt pathway in trophoblasts was significantly upregulated following IGFBP2 treatment. To confirm bioinformatics findings, we did cell-based experiments and found that treatment of inhibitors for insulin-like growth factor (IGF)-1 receptor-PI3K-Akt pathway significantly reduced IGFBP2-induced trophoblast cell proliferation and mRNA expressions of PCNA and Ki67. Our findings suggest that IGFBP2 may increase trophoblast proliferation through the PI3K-Akt signaling pathway to affect pregnancy outcomes and that IGFBP2 may be a new target for future research and treatment of RSA.
摘要：
复发性自然流产（RSA）是一种严重的疾病，对妇女的健康产生不利影响。RSA患者血浆中的差异表达蛋白（DEP）有助于寻找新的治疗靶标并通过质谱鉴定。在57个部门中，RSA中21个上调，36个下调。基因本体论分析表明，鉴定的DEP与细胞增殖有关，包括显著下调的胰岛素样生长因子结合蛋白2（IGFBP2）。使用临床蜕膜组织的免疫组织化学结果还显示，在RSA滋养细胞中IGFBP2的表达显着降低。细胞增殖实验表明，IGFBP2处理增加了滋养细胞的增殖和PCNA和Ki67的mRNA表达。转录组测序实验和京都基因和基因组百科全书分析揭示,在IGFBP2处理后,滋养细胞中PI3K-Akt途径中组分的基因表达显著上调。为了证实生物信息学的发现，我们进行了基于细胞的实验,发现胰岛素样生长因子(IGF)-1受体-PI3K-Akt通路抑制剂显著降低IGFBP2诱导的滋养细胞增殖以及PCNA和Ki67的mRNA表达.我们的研究结果表明，IGFBP2可能通过PI3K-Akt信号通路增加滋养细胞增殖，从而影响妊娠结局，IGFBP2可能成为未来研究和治疗RSA的新靶点。
