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

American Journal of Physiology - Heart and Circulatory Physiology - Tập 287 Số 1 - Trang H187-H195 - 2004
Jian‐Xiong Chen1, Ying Chen2, Laura M. DeBusk2, Wen‐Yu Lin2, Pengnain Charles Lin2
1Department of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave., Preston Research Bldg., Rm. 315, Nashville, TN 37232, USA.
2Departments of Radiation Oncology, Cell Biology, and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

Tóm tắt

Inflammation and angiogenesis are associated with pathological disorders. TNF-α is a major inflammatory cytokine that also regulates angiogenesis. TNF-α 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-α 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-α. In the absence of TNF-α, neither Ang-1 nor Ang-2 promoted corneal angiogenesis. Low doses (0–25 ng/ml) of TNF-α increased vascular branch formation of cultured endothelial cells. Overexpression of Ang-1 or Ang-2 enhanced the effects of TNF-α. These data suggest that Tie-2 signaling synergistically amplifies and participates in TNF-α-mediated angiogenesis. In addition, high doses (≥50 ng/ml) of TNF-α 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-α-induced angiogenesis, and high doses attenuate TNF-α-induced cell death. The study provides evidence supporting a role for Tie-2 in inflammatory angiogenesis.

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Thông tin xuất bản

American Journal of Physiology - Heart and Circulatory Physiology

Tập 287 Số 1

H187-H195

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