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FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds
Author(s) -
Jeon Hyeran Helen,
Yu Quan,
Lu Yongjian,
Spencer Evelyn,
Lu Chanyi,
Milovanova Tatyana,
Yang Yang,
Zhang Chenying,
Stepanchenko Olga,
Vafa Rameen P,
Coelho Paulo G,
Graves Dana T
Publication year - 2018
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5075
Subject(s) - angiogenesis , foxo1 , wound healing , vascular endothelial growth factor a , granulation tissue , cancer research , neovascularization , transcription factor , biology , immunology , microbiology and biotechnology , vascular endothelial growth factor , vegf receptors , genetics , gene
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.