Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis.

Abstract

Inflammation and angiogenesis are associated with pathological disorders. TNF-alpha is a major inflammatory cytokine that also regulates angiogenesis. TNF-alpha has been shown to regulate Tie-2 and angiopoietin (Ang) expression, but the functional significance is less clear. In this study, we showed that TNF-alpha induced a weak angiogenic response in a mouse cornea assay. Systemic overexpression of Ang-1 or Ang-2 dramatically increased corneal angiogenesis induced by TNF-alpha. In the absence of TNF-alpha, neither Ang-1 nor Ang-2 promoted corneal angiogenesis. Low doses (0-25 ng/ml) of TNF-alpha increased vascular branch formation of cultured endothelial cells. Overexpression of Ang-1 or Ang-2 enhanced the effects of TNF-alpha. These data suggest that Tie-2 signaling synergistically amplifies and participates in TNF-alpha-mediated angiogenesis. In addition, high doses (>/=50 ng/ml) of TNF-alpha induced apoptosis in endothelial cells, but addition of Ang-1 or Ang-2 significantly reduced cell death. Enhanced endothelial cell survival was correlated with Akt phosphorylation. Collectively, our data reveal dual functional roles of Tie-2: low doses enhance TNF-alpha-induced angiogenesis, and high doses attenuate TNF-alpha-induced cell death. The study provides evidence supporting a role for Tie-2 in inflammatory angiogenesis.

• Authors: Jian-Xiong Chen, Ying Chen, Laura DeBusk, Wenyu Lin, Pengnain Charles Lin
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 287 Issue 1 Pg. H187-95 (Jul 2004) ISSN: 0363-6135 [Print] United States
• PMID: 15210451 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ANGPT1 protein, human
• Angiopoietin-1
• Angiopoietin-2
• Proto-Oncogene Proteins
• Tumor Necrosis Factor-alpha
• Receptor, TIE-2
• AKT1 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Angiopoietin-1 (physiology)
• Angiopoietin-2 (physiology)
• Animals
• Apoptosis (physiology)
• Capillaries (physiology)
• Cell Survival (physiology)
• Cells, Cultured
• Endothelium, Vascular (physiology)
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Neovascularization, Physiologic (physiology)
• Protein Serine-Threonine Kinases (physiology)
• Proto-Oncogene Proteins (physiology)
• Proto-Oncogene Proteins c-akt
• Receptor, TIE-2 (physiology)
• Tumor Necrosis Factor-alpha (pharmacology)