Targeting connexin43 expression accelerates the rate of wound repair

Cindy Qiu, Petula Coutinho, Stefanie Frank, Susanne Franke, Lee-yong Law, Paul Martin, Colin R Green, David L Becker

Research output: Contribution to journalArticle (Academic Journal)peer-review

232 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1697-703
Number of pages7
JournalCurrent Biology
Volume13
Issue number19
Publication statusPublished - 30 Sep 2003

Keywords

  • Animals
  • Connexin 43
  • Down-Regulation
  • Gels
  • Immunohistochemistry
  • Inflammation
  • Mice
  • Mice, Inbred ICR
  • Neutrophils
  • Oligodeoxyribonucleotides, Antisense
  • Skin Physiological Phenomena
  • Wound Healing

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