title: The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning.
abstract: The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2, 6 hours) decreased the threshold voltage of galvanotaxis to < 25 mV/mm, whereas this value was between 25 and 50 mV/mm in the normal culture control. In a scratch-wound monolayer assay in which the applied EF was in the default healing direction, hypoxic preconditioning accelerated healing by 1.38-fold compared with the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC) abolished the enhanced galvanotaxis and the accelerated healing by hypoxic preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing.
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xupin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Ren
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Huanbo
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004560:Electricity; D019194:Ischemic Preconditioning; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D062326:Re-Epithelialization / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000293:injuries; D014945:Wound Healing / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species