Targeting connexin43 expression accelerates the rate of wound repair

Curr Biol. 2003 Sep 30;13(19):1697-703. doi: 10.1016/j.cub.2003.09.007.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Down-Regulation / drug effects*
  • Gels
  • Immunohistochemistry
  • Inflammation / drug therapy
  • Mice
  • Mice, Inbred ICR
  • Neutrophils / drug effects
  • Oligodeoxyribonucleotides, Antisense / metabolism*
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Oligodeoxyribonucleotides, Antisense / therapeutic use
  • Skin Physiological Phenomena*
  • Wound Healing / drug effects*
  • Wound Healing / genetics
  • Wound Healing / physiology


  • Connexin 43
  • Gels
  • Oligodeoxyribonucleotides, Antisense