Understanding the perspectives of forkhead transcription factors in delayed wound healing

Wound healing is a complex overlapping biological process that involves a sequence of events coordinated by various cells, proteins, growth factors, cytokines and signaling molecules. Recent evidence indicates that forkhead box O1 (FOXO1) transcription factors play an important role in organizing these events to stimulate wound healing. The ubiquitously expressed forkhead box, class O (FOXO) transcription factors act as cell signaling molecules in various transcriptional processes that are involved in diverse cellular activities, including cell death, cell differentiation, DNA repair, apoptosis, and oxidative stress in response to stimuli, and interact with numerous proteins. Due to the activation of FOXO targeted genes, FOXOs are involved in maintaining the balance between oxidative stress and antioxidants. In humans, different isoforms of FOXO namely FOXO1, FOXO3, FOXO4 and FOXO6 are present, however only FOXO1 and FOXO3 possess biological functions such as morphogenesis, maintenance and tissue regeneration. This might make FOXOs an important therapeutic target to enhance wound healing in diabetes, and to avoid over scarring. In spite of extensive literature, little is known regarding the role of FOXO and its relationship in wound healing. This review provides a summary of FOXO proteins and their biological role in wound healing and oxidative stress.