Knockdown of DVL2 inhibits vascular smooth muscle cell proliferation and migration

Despite advancements in drug-eluting stent technology, the incidence of in-stent restenosis (ISR) remains around 5–10%. The complex mechanisms of ISR are primarily based on the proliferation and migration of vascular smooth muscle cells (VSMCs). The dishevelled gene (DVL2), a component of the WNT signaling pathway, is involved in tumorigenesis. However, the role of DVL2 in ISR remains unknown. In this study, we used the rat carotid balloon injury model in vivo and PDGF-BB-treated VSMCs in vitro. Intimal hyperplasia was assessed by Hematoxylin and eosin staining. VSMCs proliferation was measured using EdU and CCK-8 assays, and migration was evaluated via transwell and Wound-healing assays. DVL2 expression was significantly increased in both balloon-injured carotid arteries and PDGF-BB-stimulated VSMCs. Knockdown of DVL2 using adeno-associated virus (AAV) effectively reduced intimal hyperplasia after balloon injury. Similarly, siRNA-mediated DVL2 silencing suppressed PDGF-BB-induced VSMCs proliferation and migration, whereas plasmid-driven DVL2 overexpression enhanced these effects. Additionally, DVL2 knockdown in PDGF-BB-stimulated VSMCs markedly upregulated the contractile markers α-smooth muscle actin and calponin. Mechanistically, DVL2 silencing inhibited β-catenin activation in PDGF-BB-treated VSMCs. Collectively, these findings demonstrated that DVL2 promoted VSMCs proliferation and migration by activating β-catenin signaling, highlighting its potential as a candidate therapeutic target for ISR.