Zonula occludens-1 (ZO-1) is an epithelial junctional protein that participates in adherens junctions (AJs) and tight junctions (TJs). In simple epithelia, ZO-1 localization shifts from AJ to TJ during the maturation of cell adhesion. We recently showed that ZO-1 is more multilayered in buccal mucosa than in skin. However, what causes this difference and how ZO-1 is spatially regulated have not been elucidated. Here we show that epithelial turnover and proliferation dictate ZO-1 distribution in the squamous epithelia. Using human oral lichen planus and mitomycin C-treated oral mucosa samples, we found that slower epithelial turnover/proliferation leads to the confinement of ZO-1 in the uppermost part of squamous epithelia. In contrast, ZO-1 is multilayered under conditions of faster cell turnover/proliferation, such as in human psoriatic skin and imiquimod-treated mouse skin. Cell culture experiments and mathematical modeling corroborated the in vivo experiments. These findings demonstrate that ZO-1 expression is dependent on epithelial cell dynamics. Our study suggests that ZO-1 distribution could be a target for therapies that aim to treat epithelial disorders.

ESDR197 - Tissue proliferation and turnover spatially regulates tight junctions in squamous epithelia

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.