Berberine inhibits Chlamydia pneumoniae infection-induced vascular smooth muscle cell migration through downregulating MMP3 and MMP9 via PI3K.
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.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Lu
L
Ma
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Lijun
L
Zhang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Beibei
B
Wang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Junyan
J
Wei
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Jingya
J
Liu
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. Electronic address: lijunwz@hotmail.com.
Lijun
L
Zhang
D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D023521:Chlamydophila Infections / Q000378:metabolism*; D016993:Chlamydophila pneumoniae; D015536:Down-Regulation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D001599:Berberine; D019869:Phosphatidylinositol 3-Kinases; D020782:Matrix Metalloproteinases
Berberine; Cell migration; Chlamydia pneumoniae; Matrix metalloproteinase; PI3K; Vascular smooth muscle cell