Arg-Gly-Asp-Ser (RGDS) is a synthetic integrin antagonist, a specific peptide motif through which extracellular matrix (ECM) components interact with integrin and can modify the behavior of cells.
Integrins mediate cell-cell and cell-extracellular matrix (ECM) interactions and recognize several ECM proteins. One of the major sites mediating integrin action is the Arg-GlyAsp (RGD) motif, present in ECM proteins and in other proteins such as disintegrins. Arg-Gly-Asp-Ser (RGDS) is a synthetic integrin antagonist, a specific peptide motif through which extracellular matrix (ECM) components interact with integrin and can modify the behavior of cells. Pretreatment with RGDS at 2.5 or 5 mg/kg, 1h before LPS, inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24h post-LPS treatment. RGDS also inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue[3]. Osteoblast-like MC3T3-E1 cells grown on the RGDS(1 and 5 mM) substrate and treated with 0.1 and 0.5 μM staurosporine showed no significant cell killing which was mediated by phosphatidylinositol 3-kinase[4]. RGDS at 500 μg/mL exhibited a dose-dependent inhibitory effect on human umbilical vein endothelial cells (HUVECs) adhesion to fibronectin and vitronectin (61% ± 4.3% and 84% ± 6.8% inhibition) and significantly reduced FGF-2–induced proliferation (50% ± 4% inhibition) in a concentration-dependent way. It was found that RGDS treatment induced caspase 8 and caspase 9 activation (1.8 ± 0.02 fold and 2.2 ± 0.2 fold versus control, respectively), while it had no effect on caspase 1 and caspase 3/7 activity[5].
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