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First published online December 11, 2006
doi: 10.1242/10.1242/jcs.03320
Research Article |
1 Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
2 Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
3 Department of Anatomy and Developmental Biology, University College of London, Gower Street, London, WC1E 6BT, UK
Author for correspondence (e-mail: d.becker{at}ucl.ac.uk)
Accepted 30 October 2006
Experimental downregulation of connexin43 (Cx43) expression at skin wound sites appears to markedly improve the rate and quality of healing, but the underlying mechanisms are currently unknown. Here, we have compared physiological and cell biological aspects of the repair process with and without Cx43 antisense oligodeoxynucleotide treatment. Treated wounds exhibited accelerated skin healing with significantly increased keratinocyte and fibroblast proliferation and migration. In vitro knockdown of Cx43 in a fibroblast wound-healing model also resulted in significantly faster healing, associated with increased mRNA for TGF-ß1, and collagen 
1 and general collagen content at the wound site. Treated wounds showed enhanced formation of granulation tissue and maturation with more rapid angiogenesis, myofibroblast differentiation and wound contraction appeared to be advanced by 2-3 days. Recruitment of both neutrophils and macrophages was markedly reduced within treated wounds, concomitant with reduced leukocyte infiltration. In turn, mRNA levels of CC chemokine ligand 2 and TNF- were reduced in the treated wound. These data suggest that, by reducing Cx43 protein with Cx43-specific antisense oligodeoxynucleotides at wound sites early in the skin healing process repair is enhanced, at least in part, by accelerating cell migration and proliferation, and by attenuating inflammation and the additional damage it can cause.
Key words: Connexin43, Gap junction, Wound healing, Inflammation, antisense
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