Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Eur J Pharmacol. 2015 May 15;755:102-9. doi: 10.1016/j.ejphar.2015.02.039. Epub 2015 Mar 3.
The mechanisms by which Chlamydia 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 C. 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 C. pneumoniae infection-induced VSMC migration and explored the possible mechanisms involved in this process. Herein, we found that C. pneumoniae 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 C. pneumoniae infection upregulated both mRNA and protein expressions of MMP3 and MMP9 (P<0.05). The specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002 significantly suppressed the increases in MMP3 and MMP9 protein expressions induced by C. pneumoniae infection (P<0.05). Further experiments showed that berberine significantly attenuated C. pneumoniae infection-induced VSMC migration (P<0.05). Moreover, berberine suppressed the protein expressions of MMP3 and MMP9 caused by C. pneumoniae infection in a dose-dependent manner (P<0.05). C. 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 C. pneumoniae infection-induced VSMC migration by downregulating the expressions of MMP3 and MMP9 via PI3K.
肺炎衣原体感染促进血管平滑肌细胞（VSMC）迁移的机制在动脉粥样硬化的发生发展中尚未完全阐明。基质金属蛋白酶（MMPs）在 VSMC 迁移中发挥重要作用。然而，目前尚不清楚 MMPs 是否参与肺炎衣原体感染诱导的 VSMC 迁移。此外，黄连素是否能发挥其对感染诱导的 VSMC 迁移的抑制作用也尚不清楚。因此，我们研究了黄连素对肺炎衣原体感染诱导的 VSMC 迁移的影响，并探讨了该过程中涉及的可能机制。在此，我们发现肺炎衣原体感染可通过 Matrigel 包被膜诱导 VSMC 迁移（P<0.05），广谱 MMP 抑制剂 GM6001 可显著抑制该迁移（P<0.05）。我们的结果还显示，肺炎衣原体感染可上调 MMP3 和 MMP9 的 mRNA 和蛋白表达（P<0.05）。特异性磷酯酰肌醇 3-激酶（PI3K）抑制剂 LY294002 显著抑制肺炎衣原体感染诱导的 MMP3 和 MMP9 蛋白表达增加（P<0.05）。进一步的实验表明，黄连素显著减弱肺炎衣原体感染诱导的 VSMC 迁移（P<0.05）。此外，黄连素呈剂量依赖性抑制肺炎衣原体感染引起的 MMP3 和 MMP9 蛋白表达（P<0.05）。肺炎衣原体感染诱导的 Akt 在 Ser473 处的磷酸化水平的增加被黄连素的处理所抑制（P<0.05）。综上所述，我们的数据表明，黄连素通过下调 MMP3 和 MMP9 的表达来抑制肺炎衣原体感染诱导的 VSMC 迁移，其机制与 PI3K 有关。
