Curcumin inhibits the proliferation and migration of vascular smooth muscle cells toy targeting the chemerin / CMKLR1 / LCN2 axis

Atherosclerosis (AS) is a chronic progressive inflammatory disease and a leading cause of death worldwide. Being a novel adipokine, chemerin is reported to be positively correlated with the severity of AS, yet its underlying mechanisms in AS remains elusive. It is well-known that AS development is significantly attributed to abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Therefore, we investigated the role of the chemerin/chemokine-like receptor 1 (CMKLR1, chemerin receptor) signaling, and the potential therapeutic effect of curcumin in VSMCs proliferation and migration during AS by establishing a high fat diet (HFD) mouse model. We found that CMKLR1 was highly expressed in HFD-induced AS tissues and that its expression level was positively correlated with aortic proliferation. Knockdown of CMKLR1 significantly inhibited VSMCs proliferation and migration, as evidenced by the EdU-incorporation assay, wound healing assay, and the induction of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9) expression. Furthermore, we discovered that Lipocalin-2 (LCN2) acts as a key factor involved in CMKLR1mediated VSMCs proliferation and migration via the p38/MAPK and Wnt/beta-catenin signaling pathways, and we demonstrated that curcumin inhibits VSMCs proliferation and migration by inhibiting chemerin/CMKLR1/LCN2, thereby reducing AS progression. Our findings suggest that chemerin/CMKLR1 activation promotes the development of AS; hence, targeting the chemerin/CMKLR1 / LCN2 signaling pathway may be a reasonable treatment modality for AS.

Automated summary

The novel adipokine chemerin is positively correlated with the severity of atherosclerosis (AS) and its underlying mechanisms in AS remain unclear. Research showed that targeting the chemerin/chemokine-like receptor 1 (CMKLR1) / Lipocalin-2 (LCN2) signaling pathway may be a reasonable treatment modality for AS, as it inhibits vascular smooth muscle cells (VSMCs) proliferation and migration through p38/MAPK and Wnt/beta-catenin signaling pathways.