Related Experiment Videos
Lipopolysaccharide activates matrix metalloproteinase-2 in endothelial cells through an NF-kappaB-dependent pathway
1National Creative Research Initiatives Center for Cardiac Regeneration and Institute of Cardiovascular Research, Chonbuk National University School of Medicine, Chonju, 560-180, Korea.
Abstract:
Vascular endothelial cells release proteinases that degrade the extracellular matrix, thus enabling cell migration during angiogenesis and vasculogenesis. Endothelial cells secrete mainly the proform of matrix metalloproteinase-2 (proMMP-2). In this report, we examined several growth factors, cytokines, and other molecules for activation of MMP-2 by human umbilical vein endothelial cells. Of these factors, we found that lipopolysaccharide (LPS) is the strongest activator of MMP-2. LPS induced MMP-2 activation in a time- and dose-dependent manner. While pretreatment with zinc chelators or nuclear factor kappaB (NF-kappaB) inhibitors suppressed LPS-induced MMP-2 activation, pretreatment with phosphatidylinositol 3'-kinase inhibitors had no effect. These results indicate that, in endothelial cells, LPS can directly enhance angiogenesis by inducing MMP-2 activation mediated through an NF-kappaB pathway.
Insights
Lipopolysaccharide (LPS) strongly activates matrix metalloproteinase-2 (MMP-2) in endothelial cells, promoting angiogenesis. This activation is dependent on the nuclear factor kappaB (NF-kappaB) pathway, highlighting a direct mechanism for LPS in enhancing blood vessel formation.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Vascular endothelial cells are crucial for angiogenesis and vasculogenesis.
- These cells secrete matrix metalloproteinase-2 (MMP-2), a key enzyme for extracellular matrix degradation and cell migration.
- Understanding MMP-2 regulation is vital for controlling vascular development.
Purpose of the Study:
- To investigate the activation of MMP-2 by various factors in human umbilical vein endothelial cells.
- To identify the strongest activator of MMP-2 among tested molecules.
- To elucidate the signaling pathways involved in LPS-induced MMP-2 activation.
Main Methods:
- Human umbilical vein endothelial cells were treated with various growth factors, cytokines, and molecules.
- Matrix metalloproteinase-2 (MMP-2) activation was measured.
- The role of zinc chelators, nuclear factor kappaB (NF-kappaB) inhibitors, and phosphatidylinositol 3'-kinase inhibitors was assessed.
Main Results:
- Lipopolysaccharide (LPS) was identified as the most potent activator of MMP-2.
- LPS-induced MMP-2 activation occurred in a time- and dose-dependent manner.
- NF-kappaB pathway inhibitors and zinc chelators suppressed LPS-induced MMP-2 activation, while PI3K inhibitors had no effect.
Conclusions:
- LPS directly enhances angiogenesis in endothelial cells by activating MMP-2.
- The NF-kappaB pathway is critical for LPS-induced MMP-2 activation.
- This study reveals a novel mechanism by which LPS influences vascular endothelial cell function.