Roles of embryonic morphogens in angiogenesis and wound healing

(1)阻断Hedgehog信号的小鼠胚胎血管生成异常Hedgehog信号包括音速Hedgehog级联信号是胚胎发生中具有代表性的形态原，但其在血管形成中的作用尚不清楚。在全胚胎培养系统中，我们研究了Hedgehog信号更黑的环丙胺处理的小鼠胚胎中的血管生成缺陷。1.卵黄囊中的血管网络异常。在E7.8-9.5期间，环丙胺处理的小鼠胚胎的卵黄囊显示未成熟的血管网络，没有重塑和动静脉分支，表明从血管生成到血管生成的转变受阻。B.未配对的背主动脉融合在E7.8-9.5期间用环丙胺处理的胚胎有未成熟的配对背主动脉，这应该在正常胚胎中进行融合。推测Shh是该表型的致病基因，而血管内皮生长因子和Notch si…与此相关。Shh.C.下游受累更多的是血管进入神经管的缺陷。在E8.5-10.2期间用环丙胺治疗时，周围的血管丛对血管进入神经管的侵袭有抑制作用。我们的结果提示血管的侵袭是由发育中的运动神经元表达的血管生成素-1介导的，其诱导依赖于从脊索和底板释放的Shh。(2)血管生成基因在扩张的毛细血管畸形中的表达变化。我们观察到，与正常张力下的病变相比，张力下扩大的病变中血管生成素-1和Tie-2基因的表达上调。未观察到形态学改变，提示扩张病变中的血管生成不是由于非特异性炎症反应，而是由于毛细血管畸形的再生。(3)bFGF治疗的压疮异位成骨是一种众所周知的胚胎形态因子，临床上用作促进创面愈合的血管生成因子。然而，碱性成纤维细胞生长因子的生物学效应如此广泛，临床上可能会出现意想不到的不良反应。在这项研究中，我们报告了两个用碱性成纤维细胞生长因子治疗的骶骨压迫性溃疡的核心，在伤口内发现了异位骨化。较少

(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