title: Hypoxia impairs skin myofibroblast differentiation and function.
abstract: Ischemic wounds are characterized by oxygen levels lower than that of healthy skin (hypoxia) and poor healing. To better understand the pathophysiology of impaired wound healing, we investigated how switching from high (21%) to low (2%) oxygen levels directly affects cultured skin myofibroblasts, essential cells for the normal wound repair process. Myofibroblast differentiation and function were assessed by quantifying α-smooth muscle actin expression and cell contraction in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2% oxygen is perceived as hypoxia and significantly reduced myofibroblast differentiation and contraction despite high levels of the profibrotic transforming growth factor-β1. Analysis of α-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded α-smooth muscle actin disassembly from stress fibers after switching from 21 to 2% oxygen. These effects were reversible by restoring high oxygen conditions and by applying mechanical stress. We suggest that mechanical challenge is a clinical relevant strategy to improve ischemic and chronic wound healing by supporting myofibroblast formation.
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
authors.forename: Ali
authors.initials: A
authors.lastname: Modarressi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pietramaggiori
authors.forename: Charles
authors.initials: C
authors.lastname: Godbout
authors.forename: Enrico
authors.initials: E
authors.lastname: Vigato
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pittet
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D040521:Subcutaneous Tissue / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D010100:Oxygen