Leptin Promotes HTR-8/SVneo Cell Invasion via the Crosstalk between MTA1/WNT and PI3K/AKT Pathways

Dis Markers. 2022 Nov 22:2022:7052176. doi: 10.1155/2022/7052176. eCollection 2022.

Abstract

The process of placental invasion is essential for a successful pregnancy. Leptin is involved in trophoblast invasiveness, and its dysregulation is connected with a series of diseases, including preeclampsia. However, the knowledge of the precise mechanisms in leptin-induced trophoblast invasiveness is still limited. According to the present research, transwell assay suggested that leptin is a dose- and time-dependent regulator in inducing HTR-8/SVneo cell invasion. Western blot analysis and immunofluorescence staining revealed that leptin-induced MMP9 expression is essential in the invasion process of HTR-8/SVneo cells. Mechanistically, we demonstrated that leptin activated β-catenin via the crosstalk between the MTA1/WNT and PI3K/AKT pathways. Besides, we showed that downregulating the key molecules in the signaling pathways by siRNA can inhibit leptin-induced MMP9 expression and further suppress invasion of HTR-8/SVneo cells. In conclusion, our study revealed a new regulatory mechanism of leptin-induced HTR-8/SVneo cell invasiveness and will provide novel insights into the causes and potential therapeutic targets for diseases related to dysregulation of trophoblast invasion in the future.

MeSH terms

  • Female
  • Humans
  • Leptin* / genetics
  • Matrix Metalloproteinase 9
  • Phosphatidylinositol 3-Kinases
  • Placenta* / physiology
  • Pregnancy
  • Proto-Oncogene Proteins c-akt
  • Repressor Proteins
  • Trans-Activators
  • Trophoblasts / physiology

Substances

  • Leptin
  • Matrix Metalloproteinase 9
  • MTA1 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Repressor Proteins
  • Trans-Activators