Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, China.
Life Sci. 2020 Nov 15;261:118351. doi: 10.1016/j.lfs.2020.118351. Epub 2020 Aug 26.
Numerous studies suggest that excessive maternal inflammation and defective extravillous trophoblast (EVT) invasion could contribute to the development of preeclampsia (PE), but the underlying mechanism remains unclear. Some evidence suggests that CyPA is elevated in PE. This research aims to investigate the effect of recombinant human CyPA on trophoblast migration and invasion both in vitro and in vivo.
We detected the expression and localization of CyPA in human placenta and explored the effects of CyPA on cell migration and invasion on HTR8/SVneo cell. Additionally, the expression levels of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway were detected. We established a mouse model by injecting pregnant mice with recombinant human CyPA and measured blood pressure, albumin/creatinine ratio, fetal and placenta weight of mice. Moreover, we examined the placental histology and MMP-2/9 and p38/ERK/JNK expression.
Our results showed that CyPA inhibited the migration and invasion of HTR8/SVneo cells in a dose-dependent manner, decreasing the expression of matrix metalloproteinase (MMP)-2/9 and molecules in the p38/ERK/JNK signaling pathway. Silencing CyPA could reverse the above effects. Moreover, CyPA could induce PE-like features in pregnant mice and disrupt the structure of the mouse placenta by reducing the junctional zone area. CyPA attenuated the trophoblast invasiveness in mice placenta by downregulating MMP-2/9 expression and p38/ERK/JNK pathway activity.
We proposed that CyPA could inhibit trophoblast migration and invasion both in vitro and in vivo, which was involved in PE development.
许多研究表明，母体过度炎症和绒毛外滋养细胞（EVT）侵袭缺陷可能导致子痫前期（PE）的发生，但潜在机制尚不清楚。有证据表明 CyPA 在 PE 中升高。本研究旨在探讨重组人 CyPA 对体外和体内滋养细胞迁移和侵袭的影响。
我们检测了 CyPA 在人胎盘组织中的表达和定位，并探讨了 CyPA 对 HTR8/SVneo 细胞迁移和侵袭的影响。此外，检测了基质金属蛋白酶（MMP）-2/9 及 p38/ERK/JNK 信号通路中分子的表达水平。我们通过向妊娠小鼠注射重组人 CyPA 建立了小鼠模型，测量了小鼠的血压、白蛋白/肌酐比、胎儿和胎盘重量。此外，我们检查了胎盘组织学和 MMP-2/9 及 p38/ERK/JNK 的表达。
我们的结果表明 CyPA 呈剂量依赖性抑制 HTR8/SVneo 细胞的迁移和侵袭，降低 p38/ERK/JNK 信号通路中 MMP-2/9 及分子的表达。沉默 CyPA 可以逆转上述作用。此外，CyPA 可通过减少连接区面积引起妊娠小鼠出现 PE 样特征，并破坏小鼠胎盘结构。CyPA 通过下调 MMP-2/9 表达和 p38/ERK/JNK 通路活性，减弱了小鼠胎盘滋养细胞的侵袭能力。
我们提出 CyPA 可抑制体外和体内滋养细胞的迁移和侵袭，这与 PE 的发生有关。
