Zonula occludens‐1 distribution and barrier functions are affected by epithelial proliferation and turnover rates

Abstract

Zonula occludens‐1 (ZO‐1) is a scaffolding protein of tight junctions, which seal adjacent epithelial cells, that is also expressed in adherens junctions. The distribution pattern of ZO‐1 differs among stratified squamous epithelia, including that between skin and oral buccal mucosa. However, the causes for this difference, and the mechanisms underlying ZO‐1 spatial regulation, have yet to be elucidated. In this study, we showed that epithelial turnover and proliferation are associated with ZO‐1 distribution in squamous epithelia. We tried to verify the regulation of ZO‐1 by comparing normal skin and psoriasis, known as inflammatory skin disease with rapid turnover. We as well compared buccal mucosa and oral lichen planus, known as an inflammatory oral disease with a longer turnover interval. The imiquimod (IMQ) mouse model, often used as a psoriasis model, can promote cell proliferation. On the contrary, we peritoneally injected mice mitomycin C, which reduces cell proliferation. We examined whether IMQ and mitomycin C cause changes in the distribution and appearance of ZO‐1. Human samples and mouse pharmacological models revealed that slower epithelial turnover/proliferation led to the confinement of ZO‐1 to the uppermost part of squamous epithelia. In contrast, ZO‐1 was widely distributed under conditions of faster cell turnover/proliferation. Cell culture experiments and mathematical modelling corroborated these ZO‐1 distribution patterns. These findings demonstrate that ZO‐1 distribution is affected by epithelial cell dynamics.

The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals

“…This hypothesis is supported by a study that describes ZO-1 redistribution in an early phase of physiologic cell shedding during intestinal cellular renewal process ( Guan et al, 2011 ). Consistently, a recent study has shown that the distribution/localization of ZO-1 can be altered during cell turnover or proliferation ( Imafuku et al, 2023 ). Other independent studies have revealed that ZO-1 can be localized in the nuclei and can regulate gene expression ( Balda et al, 2003 , Balda and Matter, 2000 , Zhong et al, 2012 ).…”

Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer

“…S100 calcium binding protein A4 (S100A4) impacts cytoskeletal dynamics and motility and is crucial for the migratory aspects of EMT ( 183 ). ZO-1 contributes to cell adhesion and polarity through its role in tight junctions ( 184 ).…”

A modified protocol for studying filaggrin degradation using a reconstructed human epidermis model under low and high humidity

“…No. ab221547) using primary antibodies (Abcam) diluted at 1:200, as described previously [10,18,20]. The ImageJ software was used to measure the area of fluorescence on at least four images for each EpiSkin specimen using a fixed threshold.…”