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

FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.

Author information

1
Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Orthodontics, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
4
Department of Stomatology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
5
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.
6
Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Beijing, PR China.
7
Biomaterials and Biomimetics, College of Dentistry, New York University, New York, NY, USA.
8
Hansjörg Wyss Department of Plastic Surgery, Langone Medical Center, New York University, New York, NY, USA.

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.

KEYWORDS:

FOXO; VEGF; angiogenesis; blood vessel; dermal; endothelial; forkhead; minipig; mucosa; skin; vascular endothelial growth factor-A; wound

PMID:
29574902
PMCID:
PMC6566901
DOI:
10.1002/path.5075
[Indexed for MEDLINE]
Free PMC Article

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