Penn Dental Researchers Identify Protein That Appears Key to Wound Healing

A University of Pennsylvania School of Dental Medicine study has identified the Foxo1 protein as being key to angiogenesis (blood vessel formation), a process that’s crucial to wound healing. The paper, “FOXO1 Regulates VEGFA Expression and Promotes Angiogenesis in Healing Wounds,” published in the Journal of Pathology, demonstrates the FOXO1 gene organizes keratinocyte activity to promote VEGFA expression and wound angiogenesis. (Editor’s note: Foxo1 refers to the protein, while the gene is designated FOXO1.)

Researchers found the density of blood vessels in healing wounds in mice lacking Foxo1 in keratinocytes was decreased by about 50% compared to mice with normal levels of the protein. Additionally, proliferating endothelial cells were decreased by 45%, and formation of new connective tissue on the surface of the wound was reduced by 50% — all of which delayed wound healing.

The investigators note that expression levels of the VEGFA protein — also important to angiogenesis — in the epithelium were significantly reduced when the FOXO1 gene was removed in these cells. In addition, they report that Foxo1 binds to the VEGFA promoter and can directly regulate its production in keratinocytes. In the next phase of research, the team plans to explore how Foxo1 functions in angiogenesis in diabetic wounds.