Abstract
Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.
Highlights
Connexins are a highly conserved group of transmembrane proteins, with 21 subtypes expressed in a human, which form gap junctions with neighbouring cells to enable intercellular communication and metabolite exchange
This review will focus on tissue-specific communication compartments during the dynamic events that occur during the regeneration and repair of epithelial tissue networks including the lung airway epithelium and the epidermis
This is most evident for Cx43 and Cx26 where alteration in the fine balance of control of expression is associated with pathological conditions including chronic non-healing wounds, psoriasis and a range of connexin-channelopathies linked with mutations in β-connexins causing skin disease [8,51]
Summary
Connexins are a highly conserved group of transmembrane proteins, with 21 subtypes expressed in a human, which form gap junctions with neighbouring cells to enable intercellular communication and metabolite exchange. Pannexins oligomerise to form channels and trafficking to the plasma membrane is dependent on interaction with the actin cytoskeleton [4,5]. Both connexins and pannexins play a key role in coordinating processes that mediate the development and maintenance of tissues in multicellular organisms. In the cardiovascular system connexins (Cxs) 37, 40, 43 and 45 are expressed In epithelial tissue, such as the airway epithelium and stratified epidermis, Cx43 is still the predominant connexin present with Cxs 26, 30 and 31 in particular emerging to play important roles as discussed below. Wound repair in the whole zebrafish model will be addressed
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