HIF‑3&alpha; affects preeclampsia development by regulating EVT growth via activation of the Flt‑1/JAK/STAT signaling pathway in hypoxia

Qu,Hongmei; Yu,Qun; Jia,Bei; Zhou,Wenzhe; Zhang,Yinghong; Mu,Linsong

doi:10.3892/mmr.2020.11701

HIF‑3α affects preeclampsia development by regulating EVT growth via activation of the Flt‑1/JAK/STAT signaling pathway in hypoxia

Authors:
- Hongmei Qu
- Qun Yu
- Bei Jia
- Wenzhe Zhou
- Yinghong Zhang
- Linsong Mu
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Affiliations: 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
Published online on: November 19, 2020 https://doi.org/10.3892/mmr.2020.11701
Article Number: 68
Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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