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      Collagen VII plays a dual role in wound healing.

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          Abstract

          Although a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin α6β4 in basal keratinocytes and negatively impacts the laminin-332/integrin α6β4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.

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          Author and article information

          Journal
          J. Clin. Invest.
          The Journal of clinical investigation
          American Society for Clinical Investigation
          1558-8238
          0021-9738
          Aug 2013
          : 123
          : 8
          Affiliations
          [1 ] Department of Dermatology, University Medical Center, Freiburg, Germany.
          Article
          68127
          10.1172/JCI68127
          3726167
          23867500
          a1156f3d-1a29-4d65-b8b3-6c890c6217ba
          History

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