Li Mo, Shen Xin, Liu Hui, Yang Bei, Lu Siying, Tang Min, Ling Yan, Li Yuezhen, Kuang Haibin
Department of Physiology, Basic Medical College, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Department of Obstetrics and Gynecology, Jiangxi Provincial People's Hospital Affiliated Nanchang University, Nanchang, Jiangxi, People's Republic of China.
J Cell Physiol. 2021 Jun;236(6):4435-4444. doi: 10.1002/jcp.30160. Epub 2020 Nov 13.
Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism.
最近，研究表明神经病变靶标酯酶（NTE）对胎盘和正常血管发育至关重要。然而，它是否参与子痫前期胎盘血管生成异常仍不清楚。因此，我们的目的是观察NTE在子痫前期胎盘中的表达及其对人脐静脉内皮细胞（HUVECs）迁移和管腔形成的影响及机制。免疫组织化学染色显示，NTE蛋白强烈定位在正常妊娠胎盘的血管中。然而，蛋白质印迹法显示子痫前期胎盘中NTE蛋白的表达水平显著降低。结果表明，与对照组和乱序短发夹RNA（shRNA）组相比，NTE过表达显著促进了HUVECs的迁移和管腔形成。相反，NTE shRNA明显抑制了HUVECs的迁移和管腔形成。此外，色谱分析证明，NTE过表达显著降低了HUVECs的磷脂酰胆碱（PC）水平，但NTE shRNA明显提高了HUVECs的PC水平。此外，外源性PC和溶血磷脂酰胆碱（LPC）以剂量依赖的方式显著抑制了HUVECs的管腔形成。总体而言，我们的结果表明，胎盘中NTE的减少可能通过PC和LPC代谢失调导致子痫前期胎盘血管生成异常。
