Lycium barbarum polysaccharide inhibits Hcy-induced vascular smooth muscle cells migration and invasion via upregulation of KLF4

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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.

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