Berberine inhibits Chlamydia pneumoniae infection-induced vascular smooth muscle cell migration through downregulating MMP3 and MMP9 via PI3K

摘要

The mechanisms by which Chlarnydia pneumoniae infection promote vascular smooth muscle cell (VSMC) migration required in the development of atherosclerosis have not yet been fully clarified. Matrix metalloproteinases (MMPs) have important roles in VSMC migration. However, it is still unknown whether MMPs are involved in Chlarnydia pneumoniae infection-induced VSMC migration. In addition, whether berberine can exert its inhibitory effects on the infection-induced VSMC migration also remains unclear. Accordingly, we investigated the effects of berberine on Chlarnydia pneumoniae infection-induced VSMC migration and explored the possible mechanisms involved in this process. Herein, we found that Chlarnydia pneurnoniae infection could induce VSMC migration through Matrigel-coated membrane (P < 0.05), which can be significantly inhibited by the broad-spectrum MMP inhibitor GM6001 (P < 0.05). Our results also showed that Chlarnydia pneumoniae infection upregulated both mRNA and protein expressions of MMP3 and MMP9 (P < 0.05). The specific phosphoinositide 3-kinase (MK) inhibitor LY294002 significantly suppressed the increases in MMP3 and MMP9 protein expressions induced by Chlarnydia pneumoniae infection (P < 0.05). Further experiments showed that berberine significantly attenuated Chlarnydia pneumoniae infection-induced VSMC migration (P < 0.05). Moreover, berberine suppressed the protein expressions of MMP3 and MMP9 caused by Chlarnydia pneumoniae infection in a dosedependent manner (P < 0.05). Chlarnydia pneumoniae infection-induced increase in the phosphorylation level of Akt at Ser473 was inhibited by the treatment with berberine (P < 0.05). Taken together, our data suggest that berberine inhibits Chlarnydia pneumoniae infection-induced VSMC migration by downregulating the expressions of MMP3 and MMP9 via PI3K. (C) 2015 Elsevier B.V. All rights reserved,