Connexins and the Epithelial Tissue Barrier: A Focus on Connexin 26

SIMPLE SUMMARY: Tissues that face the external environment are known as ‘epithelial tissue’ and form barriers between different body compartments. This includes the outer layer of the skin, linings of the intestine and airways that project into the lumen connecting with the external environment, and the cornea of the eye. These tissues do not have a direct blood supply and are dependent on exchange of regulatory molecules between cells to ensure co-ordination of tissue events. Proteins known as connexins form channels linking cells directly and permit exchange of small regulatory signals. A range of environmental stimuli can dysregulate the level of connexin proteins and or protein function within the epithelia, leading to pathologies including non-healing wounds. Mutations in these proteins are linked with hearing loss, skin and eye disorders of differing severity. As such, connexins emerge as prime therapeutic targets with several agents currently in clinical trials. This review outlines the role of connexins in epithelial tissue and how their dysregulation contributes to pathological pathways. ABSTRACT: Epithelial tissue responds rapidly to environmental triggers and is constantly renewed. This tissue is also highly accessible for therapeutic targeting. This review highlights the role of connexin mediated communication in avascular epithelial tissue. These proteins form communication conduits with the extracellular space (hemichannels) and between neighboring cells (gap junctions). Regulated exchange of small metabolites less than 1kDa aide the co-ordination of cellular activities and in spatial communication compartments segregating tissue networks. Dysregulation of connexin expression and function has profound impact on physiological processes in epithelial tissue including wound healing. Connexin 26, one of the smallest connexins, is expressed in diverse epithelial tissue and mutations in this protein are associated with hearing loss, skin and eye conditions of differing severity. The functional consequences of dysregulated connexin activity is discussed and the development of connexin targeted therapeutic strategies highlighted.