Open Access

Increased expression of IFN‑γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop

  • Authors:
    • Huiqiang Liu
    • Wenhao Wang
    • Chongdong Liu
  • View Affiliations

  • Published online on: December 2, 2020     https://doi.org/10.3892/etm.2020.9544
  • Article Number: 112
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The weakening of extravillous trophoblast (EVT) invasion results in shallow placenta implantation. In HTR8/SVneo cells, IFN‑γ can activate STAT1 and reduce cell invasion, and suppressor of cytokine signaling (SOCS) is an important negative regulatory protein in the Janus kinase (JAK)/STAT activator pathway and has a negative feedback function on JAK/STAT1. The aim of the present study was to elucidate how SOCS1 feedback regulates JAK/STAT1 and affects EVT cell invasion, which in turn affects the development of preeclampsia (PE). MTT and Annexin V/phosphatidylserine (PS) assays were performed to evaluate the viability and apoptosis of HTR8/SVneo cells treated with IFN‑γ, respectively. Wound healing and invasion assays were also conducted to measure the migratory and invasive abilities of IFN‑γ‑treated HTR8/SVneo cells. The mRNA and protein expression levels of genes were detected using reverse transcription‑quantitative PCR and western blot analysis. Small interfering RNA knockdown of SOCS1 was used to verify the role of feedback regulation in the IFN‑γ‑activated JAK/STAT1 signaling pathway. IFN‑γ can inhibit HTR8/SVneo migration and invasion, and promote apoptosis by increasing the expression of phosphorylated (p)‑JAK, p‑STAT1 and caspase3, and reducing the expression of platelet‑derived growth factor receptor A and Ezrin. Furthermore, SOCS1 may negatively regulate JAK/STAT1 and affect HTR‑8/SVneo invasiveness. Evaluation of clinical samples demonstrated that the expression levels of SOCS1 and IFN‑γ were higher in patients with PE compared with the healthy group. Collectively, the present results indicated that IFN‑γ reduced the invasion of HTR‑8/SVneo cells by activating JAK/STAT1, concurrently leading to an increase in SOCS1, which negatively regulates JAK/STAT1 and eliminates the pro‑inflammatory effects of IFN‑γ, thus forming a feedback loop.
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February-2021
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Spandidos Publications style
Liu H, Wang W and Liu C: Increased expression of IFN‑γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop. Exp Ther Med 21: 112, 2021.
APA
Liu, H., Wang, W., & Liu, C. (2021). Increased expression of IFN‑γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop. Experimental and Therapeutic Medicine, 21, 112. https://doi.org/10.3892/etm.2020.9544
MLA
Liu, H., Wang, W., Liu, C."Increased expression of IFN‑γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop". Experimental and Therapeutic Medicine 21.2 (2021): 112.
Chicago
Liu, H., Wang, W., Liu, C."Increased expression of IFN‑γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop". Experimental and Therapeutic Medicine 21, no. 2 (2021): 112. https://doi.org/10.3892/etm.2020.9544