Down-regulated expressed protein HMGB3 inhibits proliferation and migration, promotes apoptosis in the placentas of fetal growth restriction
Down-regulated expressed protein HMGB3 inhibits proliferation and migration, promotes apoptosis in the placentas of fetal growth restriction
复制标题
下调表达蛋白HMGB3抑制胎儿生长受限胎盘增殖和迁移，促进细胞凋亡
DOI：
10.1016/j.biocel.2018.11.007
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Miao, Zhijing
中科院分区：
文献类型：
--
作者：
Lv, Yan;Lv, Mingming;Miao, Zhijing
胎儿生长受限（FGR）是妊娠的主要并发症之一，可导致严重的短期和长期疾病。高迁移率族蛋白3（HMGB 3）已被发现有助于许多癌症的发展。然而，HMGB 3在FGR发病机制中的作用尚属空白。本研究采用免疫印迹法和实时定量聚合酶链反应（qRT-PCR）检测了6例正常妊娠和5例FGR患者胎盘组织中HMGB 3的表达水平。采用CCK-8法、transwell法和流式细胞术检测HMGB 3过表达和沉默对HTR 8/SVneo滋养层细胞系功能的影响。结果显示，与正常对照相比，FGR胎盘中HMGB 3的蛋白水平显著降低，而HMGB 3的mRNA水平没有显著改变。此外，HMGB 3蛋白过表达可显著促进滋养层细胞的增殖和迁移能力，抑制其凋亡能力。细胞功能实验显示，当HMGB 3表达沉默时，结果相反。qRT-PCR检测细胞功能相关基因PCNA、Ki 67、Tp 53、Bax、MMP-2和E-cadherin的表达变化。质谱分析结果表明HMGB 3可与71种蛋白质直接或间接相互作用。综上所述，HMGB 3可能在FGR的发病机制中具有重要意义，可能通过导致胎盘绒毛滋养层细胞功能障碍以及与其他蛋白质相互作用而发挥作用。
Fetal growth restriction (FGR) is one of the major complications of pregnancy, which can lead to serious short-term and long-term diseases. High-mobility group box 3 (HMGB3) has been found to contribute to the development of many cancers. However, the role of HMGB3 in the pathogenesis of FGR is blank. Here, we measured the expression level of HMGB3 in the placenta tissues of six normal pregnancies and five FGR patients by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). CCK8 assay, transwell assay and flow cytometry were used to detect the functional effects of overexpression and silencing of HMGB3 on the HTR8/SVneo trophoblast cell line. The results showed that the protein levels of HMGB3 were significantly decreased in FGR placentas compared to normal controls, while mRNA levels of HMGB3 were not significantly altered. Furthermore, when overexpressed of protein HMGB3 of the trophoblast cells, the proliferation and migration abilities were significantly promoted, and the apoptosis abilities of these cells were statistically inhibited. Cell functional experiments showed the opposite results when the expression of HMGB3 was silent. And the expression of cell function-related genes PCNA, Ki67, Tp53, Bax, MMP-2 and E-cadherin was observed to show corresponding changes by qRT-PCR. The results of mass spectrometry showed that HMGB3 may directly or indirectly interact with 71 proteins. In summary, our results indicated that HMGB3 might be of very great significance to the pathogenesis of FGR and might play the role by leading the dysfunction of placental villous trophoblast cells and through the interaction with some other proteins.