叉头框蛋白 O1（FOXO1）调控血管内皮生长因子 A（VEGFA）的表达，促进伤口愈合中的血管生成。
FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.
机构信息
Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
J Pathol. 2018 Jul;245(3):258-264. doi: 10.1002/path.5075. Epub 2018 Apr 20.
Abstract
Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound-healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
摘要
血管生成是伤口愈合的关键方面。我们研究了在转录因子 FOXO1 谱系特异性缺失的小鼠中角质形成细胞在促进血管生成中的作用。结果表明，角质形成细胞特异性缺失 Foxo1 会减少黏膜和皮肤伤口中 VEGFA 的表达，导致内皮细胞增殖减少、血管生成减少以及上皮再形成和肉芽组织形成受损。体外实验表明 FOXO1 是 VEGFA 转录和表达所必需的。在一种类似于人类愈合的猪真皮伤口愈合模型中，局部应用 FOXO1 抑制剂可减少血管生成。这是第一个报道 FOXO1 直接调节 VEGFA 表达，并且 FOXO1 是伤口愈合过程中正常血管生成所必需的。版权所有 © 2018 英国和爱尔兰病理学学会。由 John Wiley & Sons, Ltd. 出版。
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