Inhibition of SOX2 mitigates vascular calcification mediated by autophagy through Wnt signaling pathway

Abstract Background SRY-box transcription factor 2 ( SOX2 ) is implicated in diverse pathological conditions; however, its contribution to vascular calcification (VC) is not well define. This research explored the influence of SOX2 on VC and associated molecular mechanisms utilizing a β-Glycerophosphate (β-GP)-driven calcification model in human aortic vascular smooth muscle cell (HA-VSMC). Results One in vitro VC model was established by exposing HA-VSMCs to β-GP. The experimental design comprised several key groups: an untreated control, a β-GP-induced calcification model group, a group receiving β-GP and SOX2 -targeting siRNA (si- SOX2 ), a group treated with β-GP and 3-Methyladenine (3-MA), an autophagy inhibitor, and a group co-treated with β-GP, si- SOX2 , and the Wnt pathway activator BML-284. Relative to controls, the β-GP model group exhibited increased calcification, elevated protein levels of SOX2 and osteogenic markers (Runx2, BMP2), enhanced autophagic activity, reduced expression of contractile markers (SM22α, α-SMA), and suppression of Wnt pathway signaling. Transfection with si- SOX2 significantly counteracted these β-GP-induced alterations. Conversely, the beneficial impact of si- SOX2 on β-GP-induced VC was negated by BML-284-mediated activation of the Wnt pathway. Conclusion The findings indicate that suppressing SOX2 alleviates β-GP-induced VC by influencing the activation status of the Wnt pathway.