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Roles of embryonic morphogens in angiogenesis and wound healing

胚胎形态发生素在血管生成和伤口愈合中的作用

基本信息

批准号：
15390537
负责人：
NAGASE Takashi
金额：
$ 9.41万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390537/
关键词：
sonic hedgehog angiogenesis whole embryo culture angiopoietin-1 capillary malformation bFGF pressure ulcer wound healing Sonic hedgehog Angiopoietin-1 Tie2 神経管卵黄嚢血管腫

项目摘要

(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

（1）Hedgehog信号通路阻断后小鼠胚胎中的异常血管生成Hedgehog信号通路包括音刺猬级联（Sonic hedgehog cascade）是胚胎发生中的代表性形态发生因子，但其在血管生成中的作用尚不清楚。我们在全胚胎培养系统中研究了用hedgehog信号更黑的环巴胺处理的小鼠胚胎中的血管生成缺陷。a.卵黄囊中的异常血管网络在E7.8-9.5期间用环巴胺处理的小鼠胚胎中的卵黄囊显示不成熟的血管网络，没有重塑和动静脉分支，表明从血管发生到血管生成的转变受损。B.成对背侧嵴融合受损在E7.8-9.5期间用环巴胺处理的胚胎具有不成熟的成对背侧嵴，其应该在正常胚胎中融合。提示Shh是导致这种表型的原因，而VEGF和Notch是导致这种表型的原因。 ...更多信息当在E8.5-10.2期间用环巴胺处理时，血管从周围血管丛侵入神经管被抑制。我们的研究结果表明，血管侵袭是由血管生成素-1介导的表达在发育中的运动神经元，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型毛细血管畸形中的表达变化作为对血管生成的临床研究，我们探讨了血管生成基因在扩张型毛细血管畸形标本中的表达。与正常张力下的病变相比，我们观察到张力下的扩大病变中血管生成素-1和Tie-2基因表达上调。未观察到形态学变化，表明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长。（3）bFGF治疗压疮后出现异位骨化。bFGF是一种著名的胚胎形态发生素，临床上被用作促进伤口愈合的血管生成因子。然而，bFGF的生物学效应是如此广泛，临床上应该有一些意想不到的不良反应。在这项研究中，我们报告了两个中心的骶骨压力溃疡治疗碱性成纤维细胞生长因子，异位骨化的伤口内。少