Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Department of General Surgery and Pediatric Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11701. Epub 2020 Nov 20.
Preeclampsia (PE) is a common obstetric disease occurring after 20 weeks of gestation. Hypoxia‑inducible factor (HIF)‑3α potentially functions as a regulatory factor in PE development, however its specific molecular mechanism remains to be elucidated. The present study aimed to investigate the function of HIF‑3α in trophoblast cell line HTR‑8/SVneo, to provide a better understanding of the pathology and treatment of PE. Normal and PE placentas were obtained from pregnant women. HTR8/SVneo cells were cultured under the condition of normoxia or hypoxia, pretreated with or without AG490, then transfected with HIF‑3α. The gene expression levels of HIF‑3α and Fms like tyrosine kinase receptor (Flt) 1 extracted from the placentas and cells were detected by reverse transcription‑quantitative PCR, and the expression levels of proteins and Janus kinase signal transducer and activator of transcription (JAK/STAT) phosphorylation were detected by western blot analysis. Viability and apoptosis of the treated cells were assessed by MTT and flow cytometry. The results demonstrated that HIF‑3α and Flt‑1 gene expression levels of PE placentas were reduced compared with normal placentas. Under a hypoxic environment, the expression levels of HIF‑3α and Flt‑1, the phosphorylation of JAK/STAT and the cell viability of HTR8/SVneo cells were increased at first and then reduced, whereas cell apoptosis was promoted over time. Under chronic hypoxia, the expression levels of HIF‑3α and Flt‑1, JAK/STAT pathway phosphorylation and cell viability of AG490‑treated HTR8/SVneo cells were reduced, but cell apoptosis was promoted. However, the upregulation of HIF‑3α in HTR8/SVneo cells markedly reversed the effects of AG490 on the cells under hypoxia. Thus, the present study preliminarily demonstrated that HIF‑3α was involved in PE development by regulating extravillous cytotrophoblast growth via Flt‑1 and the JAK/STAT signaling pathway.
子痫前期（PE）是一种常见的产科疾病，发生于妊娠 20 周后。缺氧诱导因子 3α（HIF-3α）可能作为 PE 发展的调节因子发挥作用，但其具体的分子机制尚不清楚。本研究旨在探讨 HIF-3α在滋养细胞系 HTR-8/SVneo 中的功能，为更好地理解 PE 的发病机制和治疗方法提供依据。从孕妇中获得正常和 PE 胎盘。在常氧或缺氧条件下培养 HTR8/SVneo 细胞，用或不用 AG490 预处理，然后转染 HIF-3α。通过逆转录-定量 PCR 检测胎盘和细胞中 HIF-3α和 Fms 样酪氨酸激酶受体 1（Flt1）的基因表达水平，通过 Western blot 分析检测蛋白质和 Janus 激酶信号转导和转录激活因子（JAK/STAT）磷酸化的表达水平。通过 MTT 和流式细胞术评估处理细胞的活力和凋亡。结果表明，PE 胎盘的 HIF-3α和 Flt1 基因表达水平低于正常胎盘。在缺氧环境下，HTR8/SVneo 细胞的 HIF-3α和 Flt1 表达水平、JAK/STAT 磷酸化和细胞活力最初增加，然后减少，而细胞凋亡随时间推移而增加。在慢性缺氧下，AG490 处理的 HTR8/SVneo 细胞的 HIF-3α和 Flt1 表达水平、JAK/STAT 途径磷酸化和细胞活力降低，但细胞凋亡增加。然而，HTR8/SVneo 细胞中 HIF-3α 的上调显著逆转了缺氧下 AG490 对细胞的作用。因此，本研究初步表明，HIF-3α 通过调节 Flt1 和 JAK/STAT 信号通路调节绒毛外滋养细胞生长参与 PE 的发生发展。
