Targeting connexin43 expression accelerates the rate of wound repair.

Article English OPEN
Qiu, Cindy ; Coutinho, Petula ; Frank, Stefanie ; Franke, Susanne ; Law, Lee-yong ; Martin, Paul ; Green, Colin R ; Becker, David L (2003)
  • Publisher: Elsevier BV
  • Journal: Current Biology, volume 13, issue 19, pages 1,697-1,703 (issn: 0960-9822)
  • Related identifiers: doi: 10.1016/j.cub.2003.09.007
  • Subject: Agricultural and Biological Sciences(all) | Q | Biochemistry, Genetics and Molecular Biology(all) | R
    mesheuropmc: integumentary system

The repair of tissue damage is a key survival process in all organisms and involves the coordinated activation of several cell types. Cell-cell communication is clearly fundamental to this process, and a great deal is known about extracellular communication within the wound site via cytokines. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels also plays a major role in the wound healing process. In two different wound healing models, incisional and excisional skin lesions, we show that a single topical application of Cx43 antisense gel brings about a transient downregulation of Cx43 protein levels, and this results in a dramatic increase in the rate of wound closure. Cx43 knockdown reduces inflammation, seen both macroscopically, as a reduction in swelling, redness, and wound gape, and microscopically, as a significant decrease in neutrophil numbers in the tissue around the wound. One long-term consequence of the improved rate of healing is a significant reduction in the extent of granulation tissue deposition and the subsequent formation of a smaller, less distorted, scar. This approach is likely to have widespread therapeutic applications in other injured tissues and opens up new avenues of research into improving the wound healing process.
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