Lumican silencing ameliorates β-glycerophosphatemediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity

Adverse cardiovascular events are associated with vascular calcification (VC) process, where vascular smooth muscle cells (VSMCs) differentiate into osteoblastic phenotype and deposit hydroxyapatite crystals. Microtubule-associated protein kinesin family member 2C (KIF2C) expression is decreased obviously in VSMC during calcification induction. Accordingly, we investigate the role and potentialmechanism of KIF2C on VSMC calcification. The effects of beta-glycerophosphate (beta-GP)/KIF2C/lumican (LUM) on calcification, calcium content, alkaline phosphatase (ALP) activity, calcification-related markers, Tubulin, the ratio of polymerized (Po) to free (Fr) tubulin, as well as levels of LUM, apolipoprotein B (APOB), and KIF2C were assessed by Alizarin red S staining, calcium assay kit, ALP assay kit, Western blot, immunofluorescence, and quantitative real-time PCR. The interplay between LUM and APOB was estimated using co-immunoprecipitation and immunofluorescence. As a result, beta-GP promoted calcification of human VMSCs (HVMSCs) and repressed KIF2C expression. KIF2C overexpression reversed the effect of beta-GP on HVSMCs. LUM silencing attenuated beta-GP-induced promotion on HVSMC calcification and increased KIF2C expression by interacting with APOB. Collectively, LUM silencing can alleviate beta-GP-induced VSMC calcification through mitigating the repression of APOB on KIF2C expression.