FoxO3a depletion accelerates cutaneous wound healing by regulating epithelial‑mesenchymal transition through β‑catenin activation
- Ting Liu
- Jing‑Zhuo Huang
- Ze‑Yuan Lei
- Rong‑Shuai Yan
- Dong‑Li Fan
Affiliations: Department of Plastic and Cosmetic Surgery, The Second Affiliated Xinqiao Hospital of Army Medical University, Chongqing 400037, P.R. China
- Published online on: January 3, 2020 https://doi.org/10.3892/mmr.2020.10912
Copyright: © Liu
et al. This is an open access article distributed under the
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The hysteresis of keratinocyte (KC) re‑epithelialization is an important factor resulting in chronic wounds; however, the molecular mechanisms involved in this cellular response remain yet to be completely elucidated. The present study demonstrated the function of transcription factor Forkhead box O3a (FoxO3a) in KC growth and migration functional effects, resulting in restrained KC re‑epithelialization during wound healing. In chronic wound tissue samples, the expression of FoxO3a was significantly increased when compared with the acute wound healing group (P<0.01). Overexpressing FoxO3a significantly inhibited, whereas silencing endogenous FoxO3a enhanced, the growth and migration of HaCaT cells in vitro. Further investigation revealed that FoxO3a negatively regulated matrix metalloproteinases 1 and 9, and increased the expression of tissue inhibitor of metalloproteinase 1. In addition, the upregulation of FoxO3a retarded, whereas the downregulation of FoxO3a accelerated, transforming growth factor‑β1‑induced epithelial‑mesenchymal transition in HaCaT cells. Mechanistically, the overexpression of FoxO3a inactivated β‑catenin signaling and markedly reduced the levels of nuclear β‑catenin. These results reveal a novel mechanism of FoxO3a in regulating KC re‑epithelialization, and provide novel targets for the prevention and treatment of chronic wounds.