The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors

R Pola, LE Ling, M Silver, MJ Corbley, M Kearney… - Nature medicine, 2001 - nature.com
R Pola, LE Ling, M Silver, MJ Corbley, M Kearney, R Blake Pepinsky, R Shapiro, FR Taylor…
Nature medicine, 2001nature.com
Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial/
mesenchymal interactions during embryonic development. We found that the hedgehog-
signaling pathway is present in adult cardiovascular tissues and can be activated in vivo.
Shh was able to induce robust angiogenesis, characterized by distinct large-diameter
vessels. Shh also augmented blood-flow recovery and limb salvage following operatively
induced hind-limb ischemia in aged mice. In vitro, Shh had no effect on endothelial-cell …
Abstract
Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial/mesenchymal interactions during embryonic development. We found that the hedgehog-signaling pathway is present in adult cardiovascular tissues and can be activated in vivo. Shh was able to induce robust angiogenesis, characterized by distinct large-diameter vessels. Shh also augmented blood-flow recovery and limb salvage following operatively induced hind-limb ischemia in aged mice. In vitro, Shh had no effect on endothelial-cell migration or proliferation; instead, it induced expression of two families of angiogenic cytokines, including all three vascular endothelial growth factor-1 isoforms and angiopoietins-1 and-2 from interstitial mesenchymal cells. These findings reveal a novel role for Shh as an indirect angiogenic factor regulating expression of multiple angiogenic cytokines and indicate that Shh might have potential therapeutic use for ischemic disorders.
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