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Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell
Ying Cui1, Yin-Wei Sun, Hai-Shuang Lin
1Department of Biochemistry and Molecular Biology, Dalian Medical University, Lvshun, Dalian, 116044, People's Republic of China.
Abstract:
Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces a dose- and time-dependent increase in MMP-2 expression in rat vascular smooth muscle cells (VSMC). Treatment with either the Rho-associated protein kinase (ROCK) inhibitor Y-27632 or suppression of ROCK-1/2 by small interfering RNA technology significantly reduced the MMP-2 expression, thus suggesting that ROCK regulates such expression. Similar results were observed when VSMC were pretreated with either U0126 or SB203580, which are selective inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, respectively, thus suggesting that these kinases are important for the induction of MMP-2 expression by PDGF-BB. In conclusion, these results described a novel mechanism in atherosclerosis through PDGF-BB signaling in VSMC, in which MMP-2 expression is induced via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase phosphorylation, as well as ROCK.
Insights
Platelet-derived growth factor-BB (PDGF-BB) increases matrix metalloproteinase-2 (MMP-2) in vascular cells. This process involves Rho-associated protein kinase (ROCK) and specific kinases, offering insights into atherosclerosis mechanisms.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Atherosclerosis Research
Background:
- Matrix metalloproteinases (MMPs) are crucial in cardiovascular disease pathogenesis.
- MMP expression is modulated by growth factors, inflammatory markers, and cytokines.
Purpose of the Study:
- To investigate the role of platelet-derived growth factor-BB (PDGF-BB) in regulating MMP-2 expression in vascular smooth muscle cells (VSMC).
- To elucidate the signaling pathways, including Rho-associated protein kinase (ROCK) and mitogen-activated protein kinases (MAPKs), involved in PDGF-BB-induced MMP-2 expression.
Main Methods:
- VSMC were treated with PDGF-BB to assess MMP-2 expression.
- Inhibitors of Rho-associated protein kinase (ROCK) (Y-27632) and MAPKs (U0126, SB203580) were used.
- Small interfering RNA (siRNA) technology was employed to suppress ROCK-1/2 expression.
Main Results:
- PDGF-BB significantly increased MMP-2 expression in a dose- and time-dependent manner.
- Inhibition or suppression of ROCK markedly reduced PDGF-BB-induced MMP-2 expression.
- Inhibition of extracellular signal-regulated kinase (ERK) and p38 MAPK also attenuated MMP-2 induction, indicating their involvement.
Conclusions:
- PDGF-BB signaling in VSMC induces MMP-2 expression through a pathway involving ERK and p38 MAPK phosphorylation.
- ROCK plays a significant regulatory role in PDGF-BB-mediated MMP-2 induction.
- These findings reveal a novel mechanism contributing to atherosclerosis development.
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