Circ_0060731 通过介导 miR-21-5p-PDCD4/ESR1 通路诱导妊娠肝内胆汁淤积症胎盘滋养层细胞凋亡。
Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.
机构信息
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Experiment, The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016, China.
出版信息
Tissue Cell. 2022 Jun;76:101771. doi: 10.1016/j.tice.2022.101771. Epub 2022 Mar 5.
PURPOSE
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy complication. However, the pathogenesis of ICP is currently unclear.
METHODS
We analyzed the placenta samples of 10 normal and 10 ICP pregnant women. the expressions of circ0060731, miR-21-5p, and their downstream target genes PDCD4, ESR1, and apoptotic protein cleaved-caspase3 were detected in the cell model.
RESULTS
The expression of Circ_0060731, PDCD4, ESR1, and caspase-3 was higher in the ICP placenta tissue than in the control group, and the expression of miR-21-5p was lower in the ICP group than in the control group. In HTR8/Svneo cells treated with TCA, the expression/levels of Circ_0060731, PDCD4, ESR1, and caspase-3 were significantly higher in the ICP group than in the control group, and miR-21-5p was significantly lower in the ICP group than in the control group. Lentiviral knockdown of miR-21-5p significantly increased the expressions of its downstream genes of PDCD4 and ESR1, and also increased cell apoptosis. Overexpression of miR-21-5p significantly reduced the expression of PDCD4 and ESR1 and reduced cell apoptosis. The dual-luciferase experiment showed that both PDCD4 and ERS1 were the target genes of miR-21-5p.
CONCLUSION
Circ_0060731 mediated miR-21-5p-PDCD4/ESR1 pathway could induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy.
目的
妊娠肝内胆汁淤积症（ICP）是一种妊娠并发症。然而，ICP 的发病机制目前尚不清楚。
方法
我们分析了 10 例正常妊娠和 10 例 ICP 孕妇的胎盘样本。在细胞模型中检测了 circ0060731、miR-21-5p 及其下游靶基因 PDCD4、ESR1 和凋亡蛋白 cleaved-caspase3 的表达。
结果
ICP 胎盘组织中 Circ_0060731、PDCD4、ESR1 和 caspase-3 的表达高于对照组，而 miR-21-5p 的表达低于对照组。在 TCA 处理的 HTR8/Svneo 细胞中，ICP 组 Circ_0060731、PDCD4、ESR1 和 caspase-3 的表达/水平明显高于对照组，而 miR-21-5p 的表达明显低于对照组。慢病毒敲低 miR-21-5p 显著增加了其下游基因 PDCD4 和 ESR1 的表达，并增加了细胞凋亡。miR-21-5p 的过表达显著降低了 PDCD4 和 ESR1 的表达并减少了细胞凋亡。双荧光素酶实验表明 PDCD4 和 ERS1 均为 miR-21-5p 的靶基因。
结论
Circ_0060731 介导的 miR-21-5p-PDCD4/ESR1 通路可诱导妊娠肝内胆汁淤积症胎盘滋养细胞凋亡。
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