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

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.

IMPACT STATEMENT

• 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.

Keywords:

• placenta accreta spectrum disorders
• YKL-40
• invasion
• trophoblast
• proliferation

Acknowledgements

The authors thank the obstetric medical staff and patients who participated in the study.

Authors’ contributions

Weifang Liu and Runfang Wang conceived of the study. Suxin Liu and Xiaoqian Yin collected human tissue samples. Weifang Liu, Shengxian Li and Runfang Wang performed related experiments. Weifang Liu, Ruiling Zhang and Jia Li analysed the data and made figures. Weifang Liu wrote the first draft of the manuscript and Yan Huo performed revisions. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

This work was supported by the Hebei General Hospital Summit Plan Talent Training Project (No,2019.89) and the medical science research project of Hebei Province (No,20210160).