title: Targeting connexin43 expression accelerates the rate of wound repair.
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.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower St., WC1E 6BT London, UK.
authors.forename: Cindy
authors.initials: C
authors.lastname: Qiu
authors.forename: Petula
authors.initials: P
authors.lastname: Coutinho
authors.forename: Stefanie
authors.initials: S
authors.lastname: Frank
authors.forename: Susanne
authors.initials: S
authors.lastname: Franke
authors.forename: Lee-yong
authors.initials: LY
authors.lastname: Law
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
authors.forename: David L
authors.initials: DL
authors.lastname: Becker
mesh_terms: 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
chemical_list: D018031:Connexin 43; D005782:Gels; D020319:Oligodeoxyribonucleotides, Antisense