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.
Original language | English (US) |
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Pages (from-to) | 258-264 |
Number of pages | 7 |
Journal | Journal of Pathology |
Volume | 245 |
Issue number | 3 |
DOIs | |
State | Published - Jul 2018 |
Keywords
- FOXO
- VEGF
- angiogenesis
- blood vessel
- dermal
- endothelial
- forkhead
- minipig
- mucosa
- skin
- vascular endothelial growth factor-A
- wound
ASJC Scopus subject areas
- Pathology and Forensic Medicine