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Targeting Connexin43 Expression Accelerates the Rate of Wound Repair

2003; Elsevier BV; Volume: 13; Issue: 19 Linguagem: Inglês

10.1016/j.cub.2003.09.007

1879-0445

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

Burn Injury Management and Outcomes

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 [1Clark R.A.F. Wound repair overview and general consideration.in: Clark R.A.F. Henson P.M. The Molecular and Cellular Biology of Wound Repair. Plenum Press, New York1996Google Scholar, 2Martin P. Wound healing—aiming for perfect skin regeneration.Science. 1997; 276: 75-81Crossref PubMed Scopus (3430) Google Scholar]. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels [3White T.W. Bruzzone R. Multiple connexin proteins in single intercellular channels connexin compatibility and functional consequences.J. Bioenerg. Biomembr. 1996; 28: 339-350Crossref PubMed Scopus (169) Google Scholar, 4Willecke K. Eiberger J. Degan J. Eckardt D. Romualdi A. Guldenagel M. Deutsch U. Sohl G. Structural and functional diversity of connexin genes in the mouse and human genome.Biol. Chem. 2002; 383: 725-737Crossref PubMed Scopus (966) Google Scholar] 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.