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

Handong Yang1, Yinfang Wang, Hang Qian

  • 1Department of Cardiovascular Diseases, Renmin Hospital of Wuhan University, Wuhan City, China.

Molecules and Cells
|August 27, 2011
PubMed

Insights

Tumor necrosis factor-α (TNF-α) promotes angiogenesis by increasing Pim-3 kinase expression in endothelial cells. Silencing Pim-3 inhibits TNF-α-induced cell migration and sprouting, suggesting Pim-3 is crucial for this process.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Angiogenesis Research

Background:

  • Tumor necrosis factor-alpha (TNF-α) is implicated in inflammatory angiogenesis.
  • Pim-3 kinase, a serine/threonine kinase, is known to suppress apoptosis and is essential for endothelial cell (EC) migration.

Purpose of the Study:

  • To investigate the role of Pim-3 kinase in TNF-α-induced angiogenesis.
  • To elucidate the mechanism by which TNF-α regulates Pim-3 expression and function in ECs.

Main Methods:

  • Treatment of ECs with TNF-α.
  • Analysis of Pim-3 mRNA expression and stabilization.
  • Gene knockdown of Pim-3 using small-interfering RNA (siRNA).
  • In vitro assessment of EC membrane protrusions and migration.
  • In vivo evaluation of EC sprouting in Matrigel plugs.
  • Measurement of eNOS mRNA abundance.

Main Results:

  • TNF-α transiently increased Pim-3 mRNA expression via the Tumor necrosis factor-α receptor-1 (TNFR1) pathway.
  • TNF-α enhanced Pim-3 mRNA stabilization in ECs.
  • Pim-3 knockdown significantly impaired TNF-α-induced EC membrane protrusions in vitro.
  • Pim-3 silencing inhibited EC sprouting in vivo.
  • eNOS mRNA abundance was reduced in Pim-3-silenced ECs.

Conclusions:

  • Pim-3 kinase plays a significant role in TNF-α-induced angiogenesis.
  • The findings suggest Pim-3 is a key mediator in the TNF-α signaling pathway that promotes endothelial cell migration and sprouting.

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