IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs.
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 endothelial cell tube formation without affecting their proliferation and motility. These findings suggest that the vascular function of IL-20 involves endothelial 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.
Tritsaris
Katerina
K
Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Copenhagen 2200N, Denmark.
Myren
Maja
M
Ditlev
Sisse B
SB
Hübschmann
Martin V
MV
van der Blom
Ida
I
Hansen
Anker Jon
AJ
Olsen
Uffe B
UB
Cao
Renhai
R
Zhang
Junhang
J
Jia
Tanghong
T
Wahlberg
Eric
E
Dissing
Steen
S
Cao
Yihai
Y
D000818:Animals; D001158:Arteries / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004338:Drug Combinations; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000378:metabolism*; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism / Q000502:physiology*; D007511:Ischemia / Q000473:pathology*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D016207:Cytokines; D004338:Drug Combinations; D007378:Interleukins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D009569:Nitric Oxide; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2; D020558:GTP Phosphohydrolases; C422042:interleukin 20