Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, 238 Jingshi East Road, Jinan, 250014, Shandong, China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Street, Jinan, 250021, Shandong, China.
J Assist Reprod Genet. 2023 Jul;40(7):1573-1587. doi: 10.1007/s10815-023-02820-0. Epub 2023 May 25.
PE is a pregnancy-specific syndrome and one of the main causes of maternal, fetal, and neonatal mortality. PRDX1 is an antioxidant that regulates cell proliferation, differentiation, and apoptosis. The aim of this study is to investigate the effect of PRDX1 on the regulation of trophoblast function by affecting autophagy and oxidative stress in preeclampsia.
Western blotting, RT-qPCR, and immunofluorescence were used to examine the expression of PRDX1 in placentas. PRDX1-siRNA was transfected to knockdown PRDX1 in HTR-8/SVneo cells. The biological function of HTR-8/SVneo cells was detected by wound healing, invasion, tube formation, CCK-8, EdU, flow cytometry, and TUNEL assays. Western blotting was used to detect the protein expression of cleaved-Caspase3, Bax, LC3II, Beclin1, PTEN, and p-AKT. DCFH-DA staining was used to detect ROS levels by flow cytometry.
PRDX1 was significantly decreased in placental trophoblasts in PE patients. Following the exposure of HTR-8/SVneo cells to HO, PRDX1 expression was significantly decreased, LC3II and Beclin1 expression was notably increased, and ROS level was also markedly increased. PRDX1 knockdown impaired migration, invasion, and tube-formation abilities and promoted apoptosis, which was accompanied by an increased expression of cleaved-Caspase3 and Bax. PRDX1 knockdown induced a significant decrease in LC3II and Beclin1 expression, along with an elevated p-AKT expression and a decreased PTEN expression. PRDX1 knockdown increased intracellular ROS levels, and NAC attenuated PRDX1 knockdown-induced apoptosis.
PRDX1 regulated trophoblast function through the PTEN/AKT signaling pathway to affect cell autophagy and ROS level, which provided a potential target for the treatment of PE.
PE 是一种妊娠特异性综合征，也是孕产妇、胎儿和新生儿死亡的主要原因之一。PRDX1 是一种抗氧化剂，可调节细胞增殖、分化和凋亡。本研究旨在探讨 PRDX1 通过影响自噬和氧化应激对子痫前期滋养细胞功能的调节作用。
采用 Western blot、RT-qPCR 和免疫荧光法检测胎盘 PRDX1 的表达。用 PRDX1-siRNA 转染 HTR-8/SVneo 细胞以敲低 PRDX1。通过划痕愈合、侵袭、管形成、CCK-8、EdU、流式细胞术和 TUNEL 检测 HTR-8/SVneo 细胞的生物学功能。Western blot 检测 cleaved-Caspase3、Bax、LC3II、Beclin1、PTEN 和 p-AKT 的蛋白表达。用 DCFH-DA 染色通过流式细胞术检测 ROS 水平。
PE 患者胎盘滋养细胞中 PRDX1 表达明显降低。HTR-8/SVneo 细胞暴露于 HO 后，PRDX1 表达明显降低，LC3II 和 Beclin1 表达显著增加，ROS 水平也明显升高。PRDX1 敲低后迁移、侵袭和管形成能力受损，促进细胞凋亡，同时 cleaved-Caspase3 和 Bax 表达增加。PRDX1 敲低导致 LC3II 和 Beclin1 表达显著降低，p-AKT 表达升高，PTEN 表达降低。PRDX1 敲低增加了细胞内 ROS 水平，NAC 减弱了 PRDX1 敲低诱导的细胞凋亡。
PRDX1 通过 PTEN/AKT 信号通路调节滋养细胞功能，影响细胞自噬和 ROS 水平，为治疗 PE 提供了潜在靶点。
