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.
J Pathol. 2018 Jul;245(3):258-264. doi: 10.1002/path.5075. Epub 2018 Apr 20.
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.
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。
