title: Cooperative regulation of substrate stiffness and extracellular matrix proteins in skin wound healing of axolotls.
abstract: Urodele amphibians (Ambystoma mexicanum), unique among vertebrates, can regenerate appendages and other body parts entirely and functionally through a scar-free healing process. The wound epithelium covering the amputated or damaged site forms early and is essential for initiating the subsequent regenerative steps. However, the molecular mechanism through which the wound reepithelializes during regeneration remains unclear. In this study, we developed an in vitro culture system that mimics an in vivo wound healing process; the biomechanical properties in the system were precisely defined and manipulated. Skin explants that were cultured on 2 to 50 kPa collagen-coated substrates rapidly reepithelialized within 10 to 15 h; however, in harder (1 GPa) and other extracellular matrices (tenascin-, fibronectin-, and laminin-coated environments), the wound epithelium moved slowly. Furthermore, the reepithelialization rate of skin explants from metamorphic axolotls cultured on a polystyrene plate (1 GPa) increased substantially. These findings afford new insights and can facilitate investigating wound epithelium formation during early regeneration using biochemical and mechanical techniques.
authors.affiliation: Liver Disease Prevention and Treatment Research Foundation, Taipei 10002, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Huang
authors.affiliation: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Mu-Hui
authors.initials: MH
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Bo-Sung
authors.initials: BS
authors.lastname: Chen
authors.affiliation: Liver Disease Prevention and Treatment Research Foundation, Taipei 10002, Taiwan.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chiou
authors.affiliation: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei 10617, Taiwan ; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan ; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Hsuan-Shu
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000558:Ambystoma mexicanum / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D012867:Skin / Q000378:metabolism* / Q000503:physiopathology*; D019063:Tenascin / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D019063:Tenascin; D003094:Collagen
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