title: Connexins: sensors of epidermal integrity that are therapeutic targets.
abstract: Gap junction proteins (connexins) are differentially expressed throughout the multiple layers of the epidermis. A variety of skin conditions arise with aberrant connexin expression or function and suggest that maintaining the epidermal gap junction network has many important roles in preserving epidermal integrity and homeostasis. Mutations in a number of connexins lead to epidermal dysplasias giving rise to a range of dermatological disorders of differing severity. 'Gain of function' mutations reveal connexin-mediated roles in calcium signalling within the epidermis. Connexins are involved in epidermal innate immunity, inflammation control and in wound repair. The therapeutic potential of targeting connexins to improve wound healing responses is now clear. This review discusses the role of connexins in epidermal integrity, and examines the emerging evidence that connexins act as epidermal sensors to a variety of mechanical, temperature, pathogen-induced and chemical stimuli. Connexins thus act as an integral component of the skin's protective barrier.
authors.affiliation: Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, UK. Electronic address: patricia.martin@gcu.ac.uk.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Martin
authors.affiliation: Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, UK; Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Easton
authors.affiliation: Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, UK.
authors.forename: Malcolm B
authors.initials: MB
authors.lastname: Hodgins
authors.affiliation: Department of Life Sciences and Institute for Applied Health Research, Glasgow Caledonian University, Glasgow G4 0BA, UK.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wright
mesh_terms: D000818:Animals; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003638:Deafness / Q000188:drug therapy / Q000235:genetics*; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007057:Ichthyosis / Q000188:drug therapy / Q000235:genetics*; D007113:Immunity, Innate; D007634:Keratitis / Q000188:drug therapy / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000188:drug therapy / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009154:Mutation; D062326:Re-Epithelialization
chemical_list: D017630:Connexins
keywords: Cell signalling; Connexin; Epidermal sensor; Epidermis; Gap junction; Therapeutic target