FOXO3A Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics.

Abstract

The skin plays a protective role against harmful environmental stress such as UV rays. Therefore, the skin is constantly exposed to potential injuries, and wound healing is a vital process for the survival of all higher organisms. Wound healing is dependent on aging and metabolic status at a whole-body level. Because the FOXO family plays a role in aging and metabolism, we investigated the molecular functions of FOXO3A in skin wound healing using FoxO3amice. We observed that FoxO3amice showed accelerated skin wound healing. During wound healing, more fibroblasts accumulated at the wound edges and migrated into the wound bed in FoxO3amice. Moreover, cell migration of dermal fibroblasts isolated from FoxO3amice was significantly induced. During the in vitro cell migration, we observed accelerated mitochondrial fragmentation and decreased oxygen consumption in the mitochondria of FoxO3afibroblasts. These changes were caused by the upregulation of mitochondrial Rho GTPase 1, which is an essential mediator of microtubule-based mitochondrial motility. Mitochondrial Rho GTPase 1 inhibition significantly attenuated cell migration, mitochondrial fragmentation, and mitochondrial recruitment to the leading edge of the cells. These data indicate that FOXO3A plays a crucial role in wound healing by regulating mitochondrial dynamics.