Epidermal Tight Junctions: ZO-1 and Occludin are Expressed in Mature, Developing, and Affected Skin and In Vitro Differentiating Keratinocytes

Abstract

This study demonstrates the presence of tight junction antigens in adult and developing human epidermis. Indirect immunofluorescence labeling and immunoelectron microscopy with antibodies to ZO-1 and occludin localized tight junction components ZO-1 and occludin to a narrow zone of the granular cells of adult epidermis. Double immunolabeling for tight junction components with adherens junction or desmosome proteins suggested that occludin is more specific for tight junctions than ZO-1, which may also be associated with adherens junctions. In developing skin, tight junctions interconnected the peridermal cells, and after the fetal stratification localized to the granular cell layer. Immunolabeling of psoriasis, lichen planus, and ichthyosis vulgaris, representing aberrant differentiation of the epidermis, showed that these conditions were associated with relocation of ZO-1 and occludin to the spinous cells. Cultures of epidermal keratinocytes, which offer a useful model for the formation of cellular contacts, revealed that tight junction components, ZO-1 and occludin, displayed a marked degree of colocalization relatively late during the process when the fusion zone had assumed a linear appearance. This suggests that the formation of adherens junctions and desmosomes precedes that of tight junctions. We speculate that the epidermal barrier, isolating the human body from the external environment, is in part formed by tight junctions of stratum granulosum.

Epidermal tight junctions in health and disease

“…7 However, more conclusive evidence of epidermal TJs in human adult skin was not established until the beginning of the millennium. [8][9][10] Almost at the same time, the notion of a functional TJ barrier in mammalian epidermis was revived by the observation that epidermal permeability barrier dysfunction developed in claudin (cldn)-1 knockout and cldn-6 transgenic mice. 11,12 Unlike the simple monolayer epithelium present in the gastrointestinal tract and bronchi where each cell expresses the full range of cellular junctions (e.g., adherens junctions, desmosomes, gap junctions, TJs), the epidermis is a highly stratified structure where cells from different layers express unique combinations of junctional complexes.…”

“…3,8,10,11,[14][15][16] Intriguingly, in the epidermis, as well as in cultured primary keratinocytes, some TJ proteins (e.g., cldn-1, cldn-4 and cldn-7) can be observed in layers that are not thought to have functional TJs (Fig. 1).…”

“…A wider (e.g., more positively stained layers) expression pattern for occludin, ZO-1 and cldn-4 with both cell membrane and intracellular localization was observed in PS. 8,65,[83][84][85] Kirschner et al 65 reported reduced expression of cldn-7 at the cell-cell borders. There is currently no consensus about cldn-1 patterns as some report no differences and others show reduced expression at different strata of the epidermis.…”

Lack of Plakoglobin in Epidermis Leads to Keratoderma

“…5C). Interestingly, the wide-spreading staining of ZO-1 suggests the disturbed cell differentiation in some skin lesions or diseases (12,13). Thus, this extended ZO-1 staining seen in Jup mutant keratinocytes further reinforced the finding of disturbed epidermal differentiation in Jup mutants.…”

Solid Lipid Nanoparticles: Technological Developments and in Vivo Techniques to Evaluate Their Interaction with the Skin

“…In human epidermis, various TJ proteins have been identified, including occludin, claudins 1, 4, and 7, JAM-1 (junctional adhesion molecule-1), zonula occludens protein 1 and MUPP-1 (multi-PDZ protein-1) [Brandner et al 2006a, Brandner et al 2006b. In human skin, TJ proteins and⁄or discrete TJlike structures are found in the interfollicular epidermis as well as in the skin appendages [Pummi 2001, Wilke et al 2006, Madison 2003]. …”