State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China ; Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, China.
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
PLoS One. 2013 Dec 31;8(12):e83281. doi: 10.1371/journal.pone.0083281. eCollection 2013.
Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and associated with increased risks in fetal complications. Currently, the exact cause of this disease is unknown. In this study we aim to investigate the potential proteins in placenta, which may participate in the molecular mechanisms of ICP-related fetal complications using iTRAQ-based proteomics approach.
The iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to separate differentially expressed placental proteins from 4 pregnant women with ICP and 4 healthy pregnant women. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three apoptosis related proteins ERp29, PRDX6 and MPO that resulted from iTRAQ-based proteomics were further verified in placenta by Western blotting and immunohistochemistry. Placental apoptosis was also detected by TUNEL assay.
Proteomics results showed there were 38 differentially expressed proteins from pregnant women with ICP and healthy pregnant women, 29 were upregulated and 9 were downregulated in placenta from pregnant women with ICP. Bioinformatics analysis showed most of the identified proteins was functionally related to specific cell processes, including apoptosis, oxidative stress, lipid metabolism. The expression levels of ERp29, PRDX6 and MPO were consistent with the proteomics data. The apoptosis index in placenta from ICP patients was significantly increased.
This preliminary work provides a better understanding of the proteomic alterations of placenta from pregnant women with ICP and may provide us some new insights into the pathophysiology and potential novel treatment targets for ICP.
妊娠肝内胆汁淤积症（ICP）通常发生在妊娠晚期，并与胎儿并发症的风险增加有关。目前，这种疾病的确切原因尚不清楚。在这项研究中，我们旨在使用 iTRAQ 基于蛋白质组学的方法研究胎盘内可能参与 ICP 相关胎儿并发症分子机制的潜在蛋白。
使用 iTRAQ 分析联合液相色谱-串联质谱（LC-MS/MS）从 4 名 ICP 孕妇和 4 名健康孕妇的胎盘组织中分离差异表达的胎盘蛋白。生物信息学分析用于寻找这些差异表达蛋白参与的相对过程。从 iTRAQ 蛋白质组学中获得的三种与凋亡相关的蛋白 ERp29、PRDX6 和 MPO 通过 Western blot 和免疫组织化学进一步在胎盘组织中进行验证。通过 TUNEL 测定检测胎盘细胞凋亡。
蛋白质组学结果显示，ICP 孕妇和健康孕妇的胎盘组织中有 38 种差异表达蛋白，其中 29 种在 ICP 孕妇的胎盘组织中上调，9 种下调。生物信息学分析表明，大多数鉴定出的蛋白与特定的细胞过程功能相关，包括凋亡、氧化应激、脂质代谢。ERp29、PRDX6 和 MPO 的表达水平与蛋白质组学数据一致。ICP 患者胎盘组织中的细胞凋亡指数明显增加。
这项初步工作提供了对 ICP 孕妇胎盘蛋白质组变化的更好理解，可能为 ICP 的病理生理学和潜在的新治疗靶点提供一些新的见解。
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