title: Connexin43 plays diverse roles in co-ordinating cell migration and wound closure events.
abstract: Chronic wounds are not only debilitating to patients, but also impose a huge financial burden on healthcare providers, as current treatments are not particularly effective. Wound healing is a highly co-ordinated process involving a vast array of signalling molecules and different cell types, therefore a substantial amount of research has been carried out in the quest to develop new therapies. The gap junction (GJ) protein connexin43 (Cx43) is one of the many molecules whose expression has been found to be up-regulated in chronic wounds and as a result targeting it may have therapeutic potential. Two different approaches have been adopted to investigate this: knockdown of Cx43 using antisense oligonucleotides and connexin mimetic peptides (CMPs) which inhibit the function of Cx43 without affecting gene expression. These peptides are targeted to the C-terminal domain or the extracellular loops of Cx43 and thus are likely to function by different means. However, both block channel function and have been shown to enhance cell migration rates. In recent years, non-channel functions have emerged for Cx43, many of which are linked to cytoskeletal dynamics and the extracellular matrix (ECM), showing that Cx43 plays diverse roles in co-ordinating wound closure events. It is clear that both CMPs and antisense oligonucleotides hold therapeutic potential, however maintaining Cx43 expression may be beneficial to the cell by preserving other non-channel functions of Cx43. Recent data in the field will be discussed in this article.
authors.affiliation: *Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, U.K.
authors.forename: Claire
authors.initials: C
authors.lastname: Lorraine
authors.affiliation: *Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, U.K.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wright
authors.affiliation: *Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, U.K.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Martin
mesh_terms: D002465:Cell Movement / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology; D017629:Gap Junctions / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use; D015398:Signal Transduction; D014945:Wound Healing / Q000235:genetics*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D016376:Oligonucleotides, Antisense