Targeting connexin43 expression accelerates the rate of wound repair.
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.
Qiu
Cindy
C
Department of Anatomy and Developmental Biology, University College London, Gower St., WC1E 6BT London, UK.
Coutinho
Petula
P
Frank
Stefanie
S
Franke
Susanne
S
Law
Lee-yong
LY
Martin
Paul
P
Green
Colin R
CR
Becker
David L
DL
D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005782:Gels; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
D018031:Connexin 43; D005782:Gels; D020319:Oligodeoxyribonucleotides, Antisense