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.
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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.)
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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
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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)
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