Pim protein kinase-3 is regulated by TNF-α and promotes endothelial cell sprouting

Elsevier BV - Tập 32 - Trang 235-241 - 2011
Handong Yang1, Yinfang Wang2, Hang Qian2, Peng Zhang2, Congxin Huang1
1Department of Cardiovascular Diseases, Renmin Hospital of Wuhan University, Wuhan City, China
2Institute of Cardiovascular Science, Dongfeng Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China

Tóm tắt

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.

Tài liệu tham khảo

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