Abstract
This study examined the potential protective effects of Lycium barbarum polysaccharide (LBP) in opposing homocysteine (Hcy)-triggered vascular smooth muscle cells (VSMCs) migration and invasion. Additionally, we examined how Krüppel-like factor 4 (KLF4) participates in the underlying molecular mechanism. Primary human umbilical vein VSMCs were treated with Hcy (100 µmol/L) and divided into five groups: Control, Hcy (100 µmol/L), Hcy + 400 mg/L LBP, Hcy + 600 mg/L LBP, Hcy + 800 mg/L LBP. Cell migration was assessed by scratch assay to screen the optimal drug intervention concentration. KLF4 expression was analyzed via Western blot. Subsequently, cells were treated with Hcy+KLF4 agonist (APTO-235, AP), Hcy+KLF4 inhibitor (Kenpaullone, Ken), and Hcy + LBP+AP. Cell migration and invasion capacities were assessed via scratch assay and Transwell invasion assay. In comparison to the Control group, Hcy notably promoted VSMC migration and invasion and downregulated KLF4 expression. Both the Hcy + 600 mg/L LBP group and the Hcy + AP group exhibited reduced migration/invasion (P < 0.01 vs. Hcy) and upregulated KLF4. Conversely, Hcy + Ken increased migration/invasion and suppressed KLF4. Notably, Hcy + LBP+AP showed the strongest inhibition of migration/invasion and the highest KLF4 upregulation (P < 0.01 vs. Hcy + AP or Hcy + 600 mg/L LBP). LBP inhibits Hcy-induced VSMCs migration and invasion by upregulating KLF4, with synergistic effects observed upon KLF4 agonist co-treatment.
Data availability
All data generated or analysed during this study are included in this published article and its supplementary information files.
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Acknowledgements
We thank the Key Laboratory of Metabolic Cardiovascular Diseases Research of National Health Commission and Ningxia Key Laboratory of Vascular Injury and Repair Research for providing experimental platforms and technical support.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Ningxia Natural Science Foundation Project (2024AAC03200), Scientific Research Project of Higher Education Institutions of the Department of Education of Ningxia Hui Autonomous Region (NYG2024116), Open competition mechanism to select the best candidates for key research projects of Ningxia Medical University (XJKF240312), Ningxia University Student Science and Technology Innovation Research Project in 2025 (S202510752020).
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Xinpeng Ma：Design and implementation of experiments, participation in manuscript writing and data analysis, and responsibility for the overall framework construction of the project.Xiuyu Wang：Co-designed experiments with XM, participated in manuscript writing and partial data analysis, with contributions equivalent to Xinpeng Ma. Tingrun MoResponsible for experimental data collection, assistance with partial experimental operations, and organization of original data records.Xing Ma：Independently completed data analysis and statistics, and performed data processing and visualization using software such as GraphPad Prism 10.0.Minghao Zhang：As the corresponding author, designed the experimental protocol and guided the overall research, wrote the main text of the manuscript, and coordinated manuscript submission and academic communication.Xinpeng Ma and Xiuyu Wang contributed equally to this work.Statement: All authors reviewed the manuscript, approved the final version for publication, and are responsible for the accuracy and integrity of the research content.
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The study was approved by the Ethics Committee of Ningxia Medical University (2024-N184) and conducted by the Guide for the Care and Use of Laboratory Animals, and the reporting follows the recommendations in the ARRIVE guidelines.
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Ma, X., Wang, X., Mo, T. et al. Lycium barbarum polysaccharide inhibits Hcy-induced vascular smooth muscle cells migration and invasion via upregulation of KLF4. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41087-0
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DOI: https://doi.org/10.1038/s41598-026-41087-0
