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Treating skin wounds with osteopontin antisense

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Mending wounds quickly while keeping them scar-free is not an impossible task. Mori et al. find that shutting down a protein called osteopontin does the trick.

Scars form when the inflammatory response that protects skin wounds against invading microbes induces the release of chemokines, which recruit fibroblasts. These cells then generate swathes of collagen to provide a new matrix for epithelial cells to close the wound. But all that new collagen stands out from the surrounding skin. It is also more than a cosmetic blight: scarring in injured organs can cause organ damage when the new collagen hardens.

Mori et al. previously found that injuries healed faster, without scarring, in knockout mice that lack neutrophils, macrophages, and mast cells. These mice are unable to mount a normal inflammatory response and fail to recruit fibroblasts to the wound. The mice had lower levels of osteopontin, a structural protein required for bone formation, which is secreted by the wound fibroblasts during inflammation.

The group now finds that suppressing osteopontin alone in healing wounds accelerates repair and reduces scarring. The researchers treated skin wounds on mice with a gel containing osteopontin antisense DNA. The resulting reduction in osteopontin levels increased the regeneration of blood vessels around the wound and sped up tissue reconstruction. These wounds had a sparser collagen matrix that might allow blood vessels to grow unimpeded.

Treated wounds also contained fewer macrophages, which the authors found normally amplify osteopontin production and inflammation via cytokine secretion. The team has yet to test whether this reduction in macrophage numbers increases the risk of infection.

How osteopontin beefs up scar tissue is still unclear. The collagen matrix within the gel-treated wounds was composed of thinner collagen fibrils, suggesting that osteopontin somehow directs either the synthesis or assembly of collagen during the repair process.

http://jem.rupress.org/cgi/content/full/jem.2051iti4v1

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