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FOXO1 has a Dual Function to Promote Normal but Inhibit Diabetic Wound Healing

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Pressure Injury, Diabetes and Negative Pressure Wound Therapy

Part of the book series: Recent Clinical Techniques, Results, and Research in Wounds ((RCTRRW,volume 3))

Abstract

FOXO1 is a transcription factor that regulates cellular events, several of which are important to wound healing. When FOXO1 is specifically deleted in keratinocytes of normal wounds, the closure of the wound is impaired. In normal wounds, FOXO1 drives expression of TGFβ1 and antioxidants to facilitate keratinocyte migration. Furthermore, TGFβ1 induced by FOXO1 in keratinocytes plays an important role in promoting connective tissue wound healing. Surprisingly, when FOXO1 is deleted in diabetic wounds, the opposite occurs, and healing is accelerated. In diabetic wounds, FOXO1 is unable to induce TGFβ1 expression and instead enhances production of CCL-10, SerpinB2, and IFN36γ. Expression of the latter factors impedes keratinocyte migration at high levels. Thus, FOXO1 plays a critical role in regulating wound healing behavior of keratinocytes and has opposite functions in normal and diabetic wounds. This is due to the fact that the genes induced by FOXO1 under normal conditions differ than those induced under diabetic conditions.

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  1. Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Dana T. Graves

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  1. Tustin, CA, USA

    Melvin A. Shiffman

  2. Newport Beach, CA, USA

    Mervin Low

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Graves, D.T. (2017). FOXO1 has a Dual Function to Promote Normal but Inhibit Diabetic Wound Healing. In: Shiffman, M., Low, M. (eds) Pressure Injury, Diabetes and Negative Pressure Wound Therapy. Recent Clinical Techniques, Results, and Research in Wounds, vol 3. Springer, Cham. https://doi.org/10.1007/15695_2017_45

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