IL-1β Promotes A7r5 and HASMC Migration and Invasion via the p38-MAPK/Ang2 Pathway

Background: The migration, proliferation, and inflammatory factor secretion of vascular smooth muscle cells (VSMCs) are involved in the important pathological processes of several vascular occlusive diseases, including coronary atherosclerosis (CAS). IL-1β, as a bioactive mediator of VSMC synthesis and secretion, can promote the pathological progress of CAS. In this study, we further explored the underlying molecular mechanisms by which IL-1β regulates VSMC migration, invasion. Methods: : We pretreated A7r5 and HASMC with IL-1β for 24 hours, and measured the expression of IL-1β, PCNA, cyclin D1, MMP2 and MMP9 in the cells by Western blotting. Cell migration and invasion ability were measured by Transwell and wound healing assays. Cell viability was measured by an MTT assay. Results: : We found that IL-1β up-regulated the expression of proliferation-related proteins (PCNA and Cyclin D1) in A7r5 and HASMC, and induces the secretion of MMP2 and MMP9, promotes cell invasion and migration. In addition, in A7r5 and HASMCs treated with IL-1β, the expression of Ang2 increased in a time-dependent manner, transfection with si-Ang2 suppressed cell migration and invasion, with down-regulated MMP2 and MMP9 expression. In parallely, we further found that the p38-MAPK pathway is activated in cells induced by IL-1β, p38-MAPK inhibitors can down-regulate the expression of Ang2. Conclusions: : These data demonstrated that IL-1β promotes A7r5 and HASMC migration and invasion via the p38-MAPK/Ang2 pathway.