title: Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2.
abstract: Cell migration is an integral part of re-epithelialization during skin wound healing, a complex process involving molecular controls that are still largely unknown. Here we identify a novel role for Tcf3, an essential transcription factor regulating embryonic and adult skin stem cell functions, as a key effector of epidermal wound repair. We show that Tcf3 is upregulated in skin wounds and that Tcf3 overexpression accelerates keratinocyte migration and skin wound healing. We also identify Stat3 as an upstream regulator of Tcf3. We show that the promigration effects of Tcf3 are non-cell autonomous and occur independently of its ability to interact with β-catenin. Finally, we identify lipocalin-2 as the key secreted factor downstream of Tcf3 that promotes cell migration in vitro and wound healing in vivo. Our findings provide new insights into the molecular controls of wound-associated cell migration and identify potential therapeutic targets for the treatment of defective wound repair.
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: 1] Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [2] Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Amy T
authors.initials: AT
authors.lastname: Ku
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Nishino
authors.affiliation: 1] Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [2] Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [3] Medical Scientist Training Program, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Howard
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Rao
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Shaver
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Garcia
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Diep N
authors.initials: DN
authors.lastname: Le
authors.affiliation: 1] Verna & Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [2] Department of Molecular & Human Genetics, Baylor College of Medicine, Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Karlin
authors.affiliation: 1] Verna & Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [2] Department of Molecular & Human Genetics, Baylor College of Medicine, Baylor Plaza, BCM 505, Houston, Texas 77030, USA [3] Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [4] Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Westbrook
authors.affiliation: Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Poli
authors.affiliation: 1] Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [2] Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [3] Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [4] Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [5] Department of Dermatology, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA [6] Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, Texas 77030, USA.
authors.forename: Hoang
authors.initials: H
authors.lastname: Nguyen
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D015603:Keratinocytes; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000378:metabolism*; D062326:Re-Epithelialization / Q000235:genetics* / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D051792:Basic Helix-Loop-Helix Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D050796:STAT3 Transcription Factor; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C494087:Stat3 protein, mouse; C075668:Tcf3 protein, mouse; C071332:Lcn2 protein, mouse