Connexins in wound healing; perspectives in diabetic patients

Abstract

Skin lesions are common events and we have evolved to rapidly heal them in order to maintain homeostasis and prevent infection and sepsis. Most acute wounds heal without issue, but as we get older our bodies become compromised by poor blood circulation and conditions such as diabetes, leading to slower healing. This can result in stalled or hard-to-heal chronic wounds. Currently about 2% of the Western population develop a chronic wound and this figure will rise as the population ages and diabetes becomes more prevalent [1]. Patient morbidity and quality of life are profoundly altered by chronic wounds [2]. Unfortunately a significant proportion of these chronic wounds fail to respond to conventional treatment and can result in amputation of the lower limb. Life quality and expectancy following amputation is severely reduced. These hard to heal wounds also represent a growing economic burden on Western society with published estimates of costs to healthcare services in the region of $25B annually [3]. There exists a growing need for specific and effective therapeutic agents to improve healing in these wounds. In recent years the gap junction protein Cx43 has been shown to play a pivotal role early on in the acute wound healing process at a number of different levels [4-7]. Conversely, abnormal expression of Cx43 in wound edge keratinocytes was shown to underlie the poor rate of healing in diabetic rats, and targeting its expression with an antisense gel restored normal healing rates [8]. The presence of Cx43 in the wound edge keratinocytes of human chronic wounds has also been reported [9]. Abnormal Cx43 biology may underlie the poor healing of human chronic wounds and be amenable therapeutic intervention [7]. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Connexins and pannexins in the integumentary system: the skin and appendages

“…The structure and function of connexins in the skin has been highlighted in several recent review articles [4,[24][25][26][27][28], which detail different aspects of their roles particularly in hyperproliferative skin disorders, inflammation and wound healing events. The study of pannexins in skin is an emerging field, but the reader is directed to reviews on pannexins [13,16] and research papers examining the roles of pannexins in skin [17,29].…”

Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis

“…However, increased levels of Cx43 have been detected in pathological conditions, e.g. during wound healing in diabetic rats and humans (62)(63)(64). Consequently, cell metabolism and Cx43 appear to be interconnected.…”

Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease

“…The inhibition of Cx43 by ASODNs has been shown to dampen inflammatory responses and promote wound-healing in many tissues including central nervous system [71], skin [72][73][74], skeletal muscle [75], heart [76], smooth muscle [77,78] and vascular endothelium [79][80][81]. Moreover, there are clinical trials using topical application of a gel containing Cx43 AS-ODNs, which have shown a safe and tolerable treatment of skin wounds, venous leg ulcers and diabetic foot ulcers [71].…”