TNFαはインテグリンα3-β8を介して血管内皮細胞の管腔形成を促進する

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  • TNFα Promotes Vascular Endothelial Cell Tube Formation via Integrin α3-β8

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<p>【Aim】</p><p>The role of tumor necrosis factor (TNF)-α in angiogenesis was first reported in 1987 in a rat corneal model, but the exact mechanism is not fully understood. In this study, we investigated the mechanism of TNFα-induced tube formation in human endothelial cells.</p><p>【Method】</p><p>The mechanism of TNFα-induced tube formation was analyzed by the Matrigel assay using the human vascular endothelial cell line EA.hy926. To examine the effects of TNFα, vascular endothelial cells were stained with calcein-AM and observed under a microscope. Various gene expression levels were determined by real-time PCR, flow cytometry (FACS), and Western blot (WB). In addition, RNAi experiments were performed to investigate the involvement of integrin.</p><p>【Result】</p><p>TNFα induced endothelial tube formation in a dose-dependent manner. TNFα also significantly upregulated integrin α3 and β8 at both mRNA and protein levels, whereas other integrin subunits, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP-2 and MMP-9) were not altered at the mRNA level. In addition, TNFα-induced tube formation was effectively blocked by integrin α3 and β8 RNAi. </p><p>【Conclusion】</p><p>Our results suggest that TNFα promotes tube formation of vascular endothelial cells through integrin α3/β8, and RNAi of α3/β8 may be an inhibitor of TNFα-induced angiogenesis, and integrin α3/β8 may be a potential target for TNFα-induced angiogenic diseases.</p>

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