Editors' ChoiceWound Healing

Lucky VII? A Dual Role for Collagen in Wound Healing

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Science Translational Medicine  17 Jul 2013:
Vol. 5, Issue 194, pp. 194ec118
DOI: 10.1126/scitranslmed.3006925

A blistering skin disorder—recessive dystrophic epidermolysis bullosa—is caused by mutations in the COL7A1 gene, which encodes a chain of type VII collagen (Col-7). Such chronic wounding disorders of the skin—or others that result from diabetes, immobility, and other conditions—present a substantial medical burden, afflicting nearly 6 million patients and costing tens of billions of U.S. dollars per annum. Although tissue engineers work to develop more effective skin substitutes to treat such wounds, a greater understanding of what catalyzes wound closure and what signals cessation of wound healing is desperately needed.

Nyström et al. have now investigated the biology underlying the failure of Col-7–deficient wounds to close. Using inducible knockout mice, hypomorphs that express only one-tenth the wild-type levels of Col-7, and cell culture assays, the authors explored the effects of Col-7 deficiency on the microenvironment of skin epithelium. The authors demonstrate that diminished levels of Col-7 cause another extracellular matrix molecule, laminin-332, to accumulate, which in turn enhances α6β4 integrin expression within the epidermis. Elevated expression of these molecules impairs keratinocyte migration, hence their ability to close a wound. Col-7 plays an additional role in the dermis, influencing myofibroblast activation and immune cell clearance, both of which must occur at the right place and the right time for proper cinching of the wound and remodeling of the granulation tissue.

Is simply applying Col-7 to chronic wounds such as those caused by recessive dystrophic epidermolysis bullosa the lucky strike? Probably not. Col-7 appears to be subject to the “Goldilocks effect,” in which too little or too much will disrupt wounding. Instead, developing a way to achieve the proper levels and distribution of Col-7 should be the next step in turning the findings of Nyström et al. into an effective therapy.

A. Nyström et al., Collagen VII plays a dual role in wound healing. J. Clin. Invest., published online 8 July 2013 (10.1172/JCI68127). [Full text]

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