Roles of embryonic morphogens in angiogenesis and wound healing

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(1)Abnormal angiogenesis in the mouse embryo with blockade of hedgehog signalingHedgehog signaling including sonic hedgehog cascades is a representative morphogen in embryogenesis, however its role in angiogenesis is still unclear. We investigated angiogenesis defects in the mouse embryos treated with hedgehog signaling blacker cyclopamine in the who9le embryo culture system.a.Abnormal vascular network in the yolk sacThe yolk sac in the mouse embryo treated with cyclopamine during E7.8-9.5 showed immature vascular network without remodeling and arteriovenous branches, suggesting impaired transition from vasculogenesis to angiogenesis. Possible involvement of Indian hedgehog and downstream VEGF/Notch signaling was also suggested.b.Impaired fusion of the paired dorsal aortaeThe embryo treated with cyclopamine during E7.8-9.5 had the immature paired dorsal aortae, which should be fused in the normal embryos. It was suggested that Shh is responsible of this phenotype, and VEGF and Notch si … More gnaling are involved downstream of Shh.c.Defect of sprouting angiogenesis into the neural tube.When treated with cyclopamine during E8.5-10.2, vascular invasion into the neural tube was inhibited from the surrounding vascular plexus. Our results suggested that the vessel invasion is mediated by angiopoietin-1 expressed in the developing motor neurons, whose induction is dependent on Shh released from the notochord and the floor plate.(2)Expression changes of angiogenic genes in the expanded capillary malformation.As a clinical investigation regarding angiogenesis, we explored expression of angiogenic genes in the specimens of the capillary malformation. We observed upregulation of Angiopoietin-1 and Tie-2 gene expressions in the enlarged lesion under tension, compared to the lesion under normal tension. Morphological changes were not observed, suggesting that angiogenesis in the expanded lesion is not due to non-specific inflammatory reaction, but due to regrowth of the capillary malformation.(3)Heterotopic ossification seen in the pressure ulcer treated with bFGF.bFGF is a well-known embryonic morphogen and is utilized clinically as an angiogenic factor promoting wound healing. However, biological effects of bFGF is so broad that there should be some concern of unexpected adverse effect fused clinically. In this study, we reported two cores of sacral pressure ulcer treated with bFGF, where ectopic ossification was noted within the wound. Less