Interleukin-17 promotes proliferation, migration, and invasion of trophoblasts via regulating PPAR-γ/RXR-α/Wnt signaling

Bioengineered. 2022 Jan;13(1):1224-1234. doi: 10.1080/21655979.2021.2020468.

Abstract

To investigate the effect of Interleukin 17 (IL-17) on the invasive capacity of trophoblast cells and the underlying mechanism, we collected placental tissues samples from pregnant women with preeclampsia (PE) and healthy pregnant women. The expression levels of IL-17 mRNA and protein in tissue samples were determined using qRT-PCR and Western blot, respectively. Cell viability and cell proliferation was determined using CCK-8 assay, and colony formation assay, respectively. Cell migration and invasion capacity were determined using transwell cell migration assay. Our results showed that the mRNA expression of IL-17 was significantly increased in PE patients and may be used as a sensitive biomarker for PE (P < 0.01). IL-17 overexpression promoted cell viability, migration, and invasion of human extravillous trophoblast cell line, HTR8/SVneo; however, IL-17 knockdown inhibited these effects. Additionally, IL-17 activated PPAR-γ/RXR-α signaling pathway, which promoted proliferation, migration, and invasion of trophoblast cells. Moreover, PPAR-γ/RXR-α heterodimers activated Wnt signaling. In conclusion, our study provides evidence that IL-17 is overexpressed in PE and promotes proliferation, migration and invasion of trophoblast cells via activating PPAR-γ/RXR-α/Wnt signaling.

Keywords: Interleukin 17; PPAR-γ/RXR-α heterodimers; invasiveness; trophoblast; wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Placenta / metabolism
  • Pre-Eclampsia* / genetics
  • Pregnancy
  • RNA, Messenger / metabolism
  • Retinoid X Receptor alpha / metabolism
  • Trophoblasts*
  • Wnt Signaling Pathway / genetics

Substances

  • IL17A protein, human
  • Interleukin-17
  • PPAR gamma
  • RNA, Messenger
  • Retinoid X Receptor alpha

Grants and funding

Shijiazhuang Science and Technology Bureau Project No. 191461083 Research on the Effect of interleukin 17 on trophoblast cell invasion and Related Mechanism. Youth Science and Technology Project Number of Hebei Provincial Department of Health No. 20201400 The Influence of interleukin 17 on trophoblast and the invasion of trophoblast and its tumors.