title: Augmenting endogenous Wnt signaling improves skin wound healing.
abstract: Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2(LacZ/+) reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2(LacZ/LacZ) mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2(LacZ/LacZ) mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Jemima L
authors.initials: JL
authors.lastname: Whyte
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Smith
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Wilfred R
authors.initials: WR
authors.lastname: Manzano
authors.forename: Nick D
authors.initials: ND
authors.lastname: Evans
authors.forename: Girija R
authors.initials: GR
authors.lastname: Dhamdhere
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Fang
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Oro
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D004431:Ear, External / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D004817:Epidermis / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D018859:Hair Follicle / Q000378:metabolism; D007150:Immunohistochemistry; D008081:Liposomes; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D008081:Liposomes; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D001616:beta-Galactosidase