The Role of Poly(ADP-Ribose) Polymerase-1 in Cutaneous Wound Healing

Critical Issue: Chronic nonhealing wounds of the lower extremities resulting in major amputations are a major health problem worldwide. Significance: Diabetes and ischemia are two major etiologies of nonhealing wounds of the lower extremities. Hyperglycemia from diabetes and oxidative stress from ischemia activate polyadenosine diphosphate (ADP)-ribose polymerase-1 (PARP-1), which is a nuclear enzyme that is best known for its role in DNA repair. However, the exact function of PARP-1 in ischemic/diabetic wound healing has not been well studied. Recent Advances: Poly-ADP-ribose (PAR) polymer has been detected in the wound bed and many of the PARylation-related reactions (oxidative stress response, expression of inflammatory cytokines and chemokines, cell proliferation, and migration) are important in the wound healing process. However, the role of PARP-1 in wound healing and the potential of targeting PARP-1 therapeutically in wounds are only recently being elucidated, with much still unknown. This review summarizes the recent advances in this field, highlighting some of the mechanisms through which PARP-1 may affect normal wound closure. Future Directions: The review also presents a perspective on some of the downstream targets of PARP-1 that may be explored for their role in wound healing and discusses about the therapeutic potential of PARP inhibitors for wound healing.