p38MAPK Mediates PDGF-BB-induced MMP-2 Expression in Rat Vascular Smooth Muscle Cells
Sun Xiao
Abstract
Sun Xiao
Abstract
Aim To study the expression of matrix metalloproteinase-2( MMP-2) gene in vascular smooth muscle cells( VSMC) induced by platelet-derived growth factor BB( PDGF-BB) and the dependent signaling pathway. Methods VSMC isolated from rats were treated with PDGF-BB at different concentration and durations. The expression of MMP-2 mRNA was detected by Real-time RT-PCR. The p38 activity was detected by Western blot. Actinomycin D,SB202190 were used to investigate underlying mechanisms. Cell migration was tested by scratch. Results MMP-2 mRNA expression was up-regulated by PDGF-BB for 1 h at 10 μg / L ~ 50 μg / L,and maximally induced at 20 μg / L. The time of MMP-2 mRNA expression maximally occurred 30 min after PDGF-BB exposure. Incubation of VSMC with PDGF-BB resulted in a significant activation of p38. VSMC pretreated with actinomycin D showed a significant decrease of MMP-2 mRNA expression. SB202190 resulted in inactivation of p38,meanwhile,significantly suppressed of MMP-2 mRNA expression on PDGFBB treatment. Conclusion PDGF-BB can induce expression of MMP-2 gene and cell migration in VSMC,which can be regulated by p38 signaling pathway. This process may play a critical role in development of vascular remodeling.
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Aim To study the expression of matrix metalloproteinase-2( MMP-2) gene in vascular smooth muscle cells( VSMC) induced by platelet-derived growth factor BB( PDGF-BB) and the dependent signaling pathway. Methods VSMC isolated from rats were treated with PDGF-BB at different concentration and durations. The expression of MMP-2 mRNA was detected by Real-time RT-PCR. The p38 activity was detected by Western blot. Actinomycin D,SB202190 were used to investigate underlying mechanisms. Cell migration was tested by scratch. Results MMP-2 mRNA expression was up-regulated by PDGF-BB for 1 h at 10 μg / L ~ 50 μg / L,and maximally induced at 20 μg / L. The time of MMP-2 mRNA expression maximally occurred 30 min after PDGF-BB exposure. Incubation of VSMC with PDGF-BB resulted in a significant activation of p38. VSMC pretreated with actinomycin D showed a significant decrease of MMP-2 mRNA expression. SB202190 resulted in inactivation of p38,meanwhile,significantly suppressed of MMP-2 mRNA expression on PDGFBB treatment. Conclusion PDGF-BB can induce expression of MMP-2 gene and cell migration in VSMC,which can be regulated by p38 signaling pathway. This process may play a critical role in development of vascular remodeling.
Key concepts: Vascular smooth muscle, Platelet-derived growth factor receptor, Matrix metalloproteinase, Messenger RNA, Western blot, Gene expression, Platelet-derived growth factor, Molecular biology