The Role of Connexins in Wound Healing and Repair: Novel Therapeutic Approaches

Abstract

Gap junctions are intercellular proteins responsible for mediating both electrical and biochemical coupling through the exchange of ions, second messengers and small metabolites. They consist of two connexons, with (one) connexon supplied by each cell. A connexon is a hexamer of connexins and currently more than 20 connexin isoforms have been described in the literature thus far. Connexins have a short half-life, and therefore gap junction remodeling constantly occurs with a high turnover rate. Post-translational modification, such as phosphorylation, can modify their channel activities. In this article, the roles of connexins in wound healing and repair are reviewed. Novel strategies for modulating the function or expression of connexins, such as the use of antisense technology, synthetic mimetic peptides and bioactive materials for the treatment of skin wounds, diabetic and pressure ulcers as well as cornea wounds, are considered.

Scars or Regeneration?—Dermal Fibroblasts as Drivers of Diverse Skin Wound Responses

“…Gap junctions are connexin channels formed between cell membranes that enable direct cytoplasmic coupling between cells, permitting intercellular passage of ions and small molecules such as Ca 2+ , ATP, and cAMP [67,68]. The major connexin expressed in mammalian skin is Connexin-43 (Cx43) [67], which has been shown to regulate and orchestrate fibroblast cellular adhesion and communication; thus, Cx43 is involved in wound healing and scar formation [69]. Cx43 deficiency or downregulation using antisense oligonucleotides accelerated wound closure in mice [70,71] and attenuated a rat model of diabetic wounds [72].…”

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

“…During wound healing, phosphorylation may also play a role in coordinating GJIC and connexin redistribution [ 245 , 246 , 247 ]. Initial responses to wounding include a generalized loss in Cx43, which may be modulated by increases in cyclic adenosine monophosphate (cAMP).…”

Review: Multimodal bioactive material approaches for wound healing

“…59 The gap junction protein connexin 43 (Cx43) has roles in wound healing, re-epithelialization, and ECM composition. 60 A small Cx43 mimetic peptide immobilized in 20% pluronic acid produced more evenly distributed vasculature and epidermal rete ridges and less granulation tissue, suggestive of low scar formation [ Figs. 3(b) and 3(c)].…”