期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 39, 页码 15364-15369出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707302104
关键词
arteriogenesis; collateral growth; therapeutical angiogenesis; ischemia
Successful therapeutic angiogenesis for the treatment of ischemic disorders relies on selection of optimal proangiogenic or arteriogenic agents that are able to promote establishment of functional collateral networks. Here, we show that IL-20, a pleiotropic inflammatory cytokine, displays an imperative effect on vascular remodeling. Stimulation of both large and microvascular endothelial cells with IL-20 leads to activation of receptor-dependent multiple intracellular signaling components, including increased phosphorylation levels of JAK2/STAT5, Erk1/2, and Akt; activation of small GTP-binding proteins Rac and Rho; and intracellular release of calcium. Surprisingly, IL-20 significantly promotes enclothelial cell tube formation without affecting their proliferation and motility. These findings suggest that the vascular function of IL-20 involves enclothelial cell organization, vessel maturation, and remodeling. Consistent with this notion, delivery of IL-20 to the ischemic muscle tissue significantly improves arteriogenesis and blood perfusion in a rat hind-limb model. Our findings provide mechanistic insights on vascular functions of IL-20 and define therapeutic implication of this cytokine for the treatment of ischemic disorders.
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