FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.
Hyeran Helen JeonQuan YuYongjian LuEvelyn SpencerChanyi LuTatyana MilovanovaYang YangChenying ZhangOlga StepanchenkoRameen P VafaPaulo G CoelhoDana T GravesPublished in: The Journal of pathology (2018)
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.
Keyphrases
- wound healing
- transcription factor
- poor prognosis
- pi k akt
- signaling pathway
- endothelial cells
- cell proliferation
- dna binding
- vascular endothelial growth factor
- randomized controlled trial
- long non coding rna
- binding protein
- type diabetes
- metabolic syndrome
- systematic review
- adipose tissue
- genome wide identification
- skeletal muscle
- high speed
- wild type