FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds

Hyeran Helen Jeon, Quan Yu, Yongjian Lu, Evelyn Spencer, Chanyi Lu, Tatyana Milovanova, Yang Yang, Chenying Zhang, Olga Stepanchenko, Rameen P. Vafa, Paulo Coelho, Dana T. Graves

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalJournal of Pathology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Wound Healing
Keratinocytes
Re-Epithelialization
Skin
Angiogenesis Inhibitors
Granulation Tissue
Transcription Factors
Swine
Endothelial Cells
Cell Proliferation
Wounds and Injuries
In Vitro Techniques

Keywords

  • Angiogenesis
  • Blood vessel
  • Dermal
  • Endothelial
  • Forkhead
  • FOXO
  • Minipig
  • Mucosa
  • Skin
  • Vascular endothelial growth factor-A
  • VEGF
  • Wound

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Jeon, H. H., Yu, Q., Lu, Y., Spencer, E., Lu, C., Milovanova, T., ... Graves, D. T. (Accepted/In press). FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds. Journal of Pathology. https://doi.org/10.1002/path.5075

FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds. / Jeon, Hyeran Helen; Yu, Quan; Lu, Yongjian; Spencer, Evelyn; Lu, Chanyi; Milovanova, Tatyana; Yang, Yang; Zhang, Chenying; Stepanchenko, Olga; Vafa, Rameen P.; Coelho, Paulo; Graves, Dana T.

In: Journal of Pathology, 01.01.2018.

Research output: Contribution to journalArticle

Jeon, HH, Yu, Q, Lu, Y, Spencer, E, Lu, C, Milovanova, T, Yang, Y, Zhang, C, Stepanchenko, O, Vafa, RP, Coelho, P & Graves, DT 2018, 'FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds', Journal of Pathology. https://doi.org/10.1002/path.5075
Jeon, Hyeran Helen ; Yu, Quan ; Lu, Yongjian ; Spencer, Evelyn ; Lu, Chanyi ; Milovanova, Tatyana ; Yang, Yang ; Zhang, Chenying ; Stepanchenko, Olga ; Vafa, Rameen P. ; Coelho, Paulo ; Graves, Dana T. / FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds. In: Journal of Pathology. 2018.
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