FoxO3a Plays a Role in Wound Healing by Regulating Fibroblast Mitochondrial Dynamics.
| Autor: | Moriyama M; Pharmaceutical Research and Technology Institute, Kindai University, Higashi-Osaka, Osaka, Japan. Electronic address: mariko@phar.kindai.ac.jp., Mori R; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan., Hayakawa T; Pharmaceutical Research and Technology Institute, Kindai University, Higashi-Osaka, Osaka, Japan., Moriyama H; Pharmaceutical Research and Technology Institute, Kindai University, Higashi-Osaka, Osaka, Japan. Electronic address: moriyama@phar.kindai.ac.jp. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of investigative dermatology [J Invest Dermatol] 2024 Nov 13. Date of Electronic Publication: 2024 Nov 13. |
| DOI: | 10.1016/j.jid.2024.10.600 |
| Abstrakt: | The skin plays a protective role against harmful environmental stress such as ultraviolet 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 forkhead box O (FOXO) family plays a role in aging and metabolism, we investigated the molecular functions of FOXO3a in skin wound healing using FoxO3a -/- mice. We observed that FoxO3a -/- mice showed accelerated skin wound healing. During wound healing, more fibroblasts accumulated at the wound edges and migrated into the wound bed in FoxO3a -/- mice. Moreover, cell migration of dermal fibroblasts isolated from FoxO3a -/- mice was significantly induced. During the in vitro cell migration, we observed accelerated mitochondrial fragmentation and decreased oxygen consumption in the mitochondria of FoxO3a -/- fibroblasts. These changes were caused by the upregulation of mitochondrial Rho GTPase 1 (Miro1), which is an essential mediator of microtubule-based mitochondrial motility. Miro1 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. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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