Aim-Gap-junctional connexin43 (Cx43) has roles in multiple aspects of skin wound healingincluding scarring. The aim here was to study the effects of a cell-permeant peptide from the Cx43 carboxyl-terminus (CT) on scarring and regeneration following cutaneous injury.
Materials & methods-The effects of Cx43 CT peptide were studied in mouse and pig models of cutaneous injury. The parameters assessed included neutrophil density, wound closure, granulation, regeneration and skin tensile properties.
Results-Cx43CT-peptide prompted decreases in area of scar progenitor tissue and promoted restoration of dermal histoarchitecture and mechanical strength following wounding of skin. These changes in healing were preceded by peptide-induced reduction in inflammatory neutrophil infiltration and alterations in the organization of epidermal Cx43, including increased connexon aggregation.
Conclusion-Cx43CT peptide promotes regenerative healing of cutaneous wounds and may have applications in tissues other than skin, including heart, cornea and spinal cord.
KeywordsCx43; gap junctions; regenerative medicine; scar prevention; wound healing Correspondence to: Robert G Gourdie.
Future perspectiveScarring and abrogated histocomplexity are normal sequalae of trauma, including that resulting from implanted materials such as tissueengineered scaffolds [55]. In ongoing work we are testing whether Cx43 CT peptides have therapeutic applications in implant biocompatibility, as well as in promoting regenerative healing of injured heart, cornea, retina and spinal cord.
Ethical conduct of researchThe authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
NIH Public Access Author ManuscriptRegen Med. Author manuscript; available in PMC 2010 January 1.
NIH-PA Author ManuscriptNIH-PA Author Manuscript
NIH-PA Author ManuscriptThe gap junction (GJ) is an aggregate of intercellular channels that provides for direct cell-tocell interchange of metabolites, ions and other small molecules of approximately 1000 Da or less [1,2]. The individual channels of GJ aggregates in vertebrates are composed of integral membrane proteins encoded by the connexin family of genes, of which more than 20 members have been recognized [3]. It is well established that GJs, and the connexin subunits of GJs, function in various aspects of wound healing [4][5][6]. Reports for such functions have included roles for GJs and connexins in intercellular spread of injury signal, immune cell extravasation, inflammation, re-epithelization, wound closure and formation of the scar progenitor, granulation tissue. Intercellular communication is thought to be one aspect of GJ-based mechanisms regulating and affecting the response of tissues to injury [4,[6][7][8][9][10]. There is also mounting evidence th...