YKL-40 promotes proliferation and invasion of HTR-8/SVneo cells by activating akt/MMP9 signalling in placenta accreta spectrum disorders

J Obstet Gynaecol. 2023 Dec;43(1):2211681. doi: 10.1080/01443615.2023.2211681.

Abstract

YKL-40 is a secreted glycoprotein that can promote invasion, angiogenesis and inhibit apoptosis, and was highly expressed in a variety of tumours. In this paper, we investigated the impacts of YKL-40 on proliferation and invasion in HTR-8/SVneo cells during placenta accreta spectrum disorders (PAS) development. The levels of YKL-40 protein in late-pregnant placental tissue were detected using immunohistochemistry and Western blotting, and gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion and apoptosis abilities of HTR-8/SVneo cells were detected by cell counting kit-8 (CCK-8), Transwell, scratch assay, and flow cytometry, respectively. Our current results showed that YKL-40 was significantly increased in the PAS group compared to the normal control group (P < 0.01). Biological function experiments showed that YKL-40 significantly promoted the proliferation, migration and invasion of HTR-8/SVneo cells, and inhibited cell apoptosis. Knockdown of YKL-40 inhibited the activation of Akt/MMP9 signalling in trophoblast cells. These data suggested that YKL-40 might be involved in the progression of PAS, which may be attributed to the regulation of Akt/MMP9 signalling pathway.

Keywords: YKL-40; invasion; placenta accreta spectrum disorders; proliferation; trophoblast.

Plain language summary

What is already known on this subject? YKL-40 is a secretory glycoprotein that can promote invasion, angiogenesis, and inhibit apoptosis and was highly expressed in a variety of tumours. Trophoblast cells resemble tumour cells in their migration and invasion.What the results of this study add? YKL-40 expression was significantly up-regulated in PAS. CCK-8 assays showed that YKL-40 remarkably enhanced the viability of HTR-8/SVneo cells. Scratch and Transwell assays demonstrated that YKL-40 significantly promoted the migration and invasion of HTR-8/SVneo cells. Additionally, YKL-40 attenuated apoptosis in HTR-8/SVneo cells.What the implications are of these findings for clinical practice and/or further research? Akt/MMP9 was involved in the regulation of YKL-40 on trophoblast invasion, which may provide theoretical basis and new ideas for the drug blocking intervention of placenta accreta.

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Chitinase-3-Like Protein 1
  • Female
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Placenta / pathology
  • Placenta Accreta* / pathology
  • Pre-Eclampsia* / genetics
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Trophoblasts / pathology

Substances

  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9
  • Chitinase-3-Like Protein 1
  • MMP9 protein, human