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KMID : 0578320110320030235
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Molecules and Cells
2011 Volume.32 No. 3 p.235 ~ p.241
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Pim Protein Kinase-3 Is Regulated by TNF-α and Promotes Endothelial Cell Sprouting
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Handong Yang
Yinfang Wang
Hang Qian
Peng Zhang
Congxin Huang
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Abstract
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Tumor necrosis factor-α (TNF-α) plays an important role in pathological angiogenesis associated with inflammatory response. Pim-3 kinase belonging to serine/threonine protein kinases is a potent suppressor of myc-induced apoptosis. We have recently demonstrated that Pim-3 plays an essential role in endothelial cell (EC) spreading and migration. In this study, we showed that TNF-α transiently increased Pim-3 mRNA expression, and this was mediated through Tumor necrosis factor-α receptor-1 (TNFR1) pathway in ECs. TNF-α could promote stabilization of Pim-3 mRNA in ECs. Small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired TNF-α-induced formation of EC membrane protrusions in vitro. Furthermore, Pim-3 silencing inhibited EC sprouting in subcutaneous Matrigel in vivo. eNOS mRNA abundance was lower in Pim-3 siRNA transfected ECs compared with the control ECs. These observations suggest that Pim-3 plays a role in TNF-α-induced angiogenesis.
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KEYWORD
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angiogenesis, endothelial cell, Pim-3, TNF-α
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