Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310000, Zhejiang Province, China.
The Affiliated Wuxi Matemity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, China.
Arch Biochem Biophys. 2019 Nov 15;676:108125. doi: 10.1016/j.abb.2019.108125. Epub 2019 Oct 3.
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder occurred in pregnant women, and the mechanism for such disease is still unclear. The bioinformatics analysis of our previous study has revealed the abnormal expression of endoplasmic reticulum protein 29 (ERp29) in placental tissue of ICP patients. In this study, the function of ERp29 was further explored using in vitro model of ICP. The results showed that up-regulation of ERp29 occurred in TCA (taurocholic acid)-treated human trophoblast HTR-8/SVeno cells, and ERp29 inhibition reversed TCA toxicity via attenuating G2/M arrest and cell apoptosis. Mechanical study revealed ERp29 inhibition suppressed phosphorylation and kinase activity of p38, thus subsequently affecting expression and phosphorylation of p53 (ser18) as well as the transcriptional activity of p53. The conduction of this study might confirm the important role of ERp29 in ICP and which would be helpful for the development of target therapeutic method for ICP.
妊娠肝内胆汁淤积症（ICP）是一种发生在孕妇中的肝脏疾病，其发病机制尚不清楚。我们之前的研究通过生物信息学分析发现，内质网蛋白 29（ERp29）在 ICP 患者的胎盘组织中表达异常。在本研究中，我们使用 ICP 的体外模型进一步探索了 ERp29 的功能。结果表明，TCA（牛磺胆酸）处理人滋养层 HTR-8/SVeno 细胞时 ERp29 上调，ERp29 抑制通过减弱 G2/M 阻滞和细胞凋亡逆转 TCA 毒性。力学研究表明，ERp29 抑制 p38 的磷酸化和激酶活性，从而影响 p53（丝氨酸 18）的表达和磷酸化以及 p53 的转录活性。本研究的开展可能证实了 ERp29 在 ICP 中的重要作用，这将有助于开发针对 ICP 的靶向治疗方法。
