Skin provides a first line of defence against viruses, bacteria and parasites that might otherwise make people ill. When an injury breaks that barrier, a systematic chain of molecular signalling launches to close the wound and re-establish the skin's layer of protection.
Senior author Dana Graves, professor in Penn Dental Medicine's Department of Periodontics, collaborated with Penn's Bhaskar Ponugoti, Fanxing Xu, Chenying Zhang, Chen Tian and Sandra Pacio, to investigate the role of FOX01 in wound healing.
Graves and colleagues bred mice that lacked the protein in their keratinocytes and then observed the wound healing process in these mice compared to mice with normal FOX01.
The mice that lacked FOX01 showed significant delays in healing. Whereas all wounds on control mice were healed after one week, all of the experimental mice still had open wounds.
The researchers examined the effect of reducing FOX01 levels on other genes known to play a role in cell migration. They found that many of these genes were significantly reduced, notably TGF-beta1, a critical growth factor in wound repair.
When the team added TGF-beta1 to cells lacking FOX01, the cells behaved normally and produced the proper suite of molecules needed for healing, indicating that FOX01 acts upstream of TGF-beta1 in the signalling pathway triggered during the healing process.
Further experimenting revealed that mice lacking FOX01 had evidence of increased oxidative stress, which is detrimental to wound healing.
The study's findings demonstrate that FOX01 plays an integral role in two key processes in wound healing: activation of TGF-beta1 and protecting the cell against oxidative damage. Its involvement in these aspects of healing make it a potential target for pharmaceuticals that could help speed healing.
The study is published in the Journal of Cell Biology.