Hypoxia impairs skin myofibroblast differentiation and function

Article Article scientifique Article Hypoxia impairs skin myofibroblast differentiation and function eng 2010 author Modarressi Ali author Pietramaggiori Giorgio 667254 author Godbout Charles 700008 author Vigato Enrico 684914 author Pittet Brigitte author Hinz Boris 514150 2818-2827 10.1038/jid.2010.224 20686497 0022-202X http://www.nature.com/jid/journal/v130/n12/full/jid2010224a.html 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 alpha-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-beta1. Analysis of alpha-smooth muscle actin expression on wrinkling substrates over time showed that reduced myofibroblast contraction preceded alpha-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. Animals Anoxia/metabolism/ pathology/physiopathology Cell Differentiation/physiology Cell Division/physiology Cells, Cultured Fibroblasts/cytology/ metabolism Humans Ischemia/metabolism/pathology/physiopathology Oxygen/ metabolism/pharmacology Rats Skin/injuries/metabolism/pathology Subcutaneous Tissue/physiology Wound Healing/ physiology Wounds and Injuries/metabolism/ pathology/physiopathology Dewey 617 57 Département de chirurgie 222 false 72 Groupe Pittet Cuenod Brigitte (chirurgie plastique et reconstructive) 96 Journal of investigative dermatology 130 12 28aa89b7-607f-4e34-944d-0a0df292bc9a Article Restricted file1.pdf 12930146 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Hypoxia impairs skin myofibroblast differentiation and function	Journal of investigative dermatology			2010	598	1

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Godbout, Charles