Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

Abstract

Bicellular tight junctions are multiprotein complexes that are required for maintenance of barrier function and fence function in epithelial tissues. Wound healing in the oral cavity leads to minimal scar formation compared to the skin, and the precise mechanisms for this regenerative response remain to be elucidated. We hypothesized that oral and skin tissues express a different tight junction repertoire both at baseline and during the wound healing response, and that these molecules may be critical to the differential repair between the two tissues. We re-analyzed a mouse skin and palate epithelium microarray dataset to identify the tight junction repertoire of these tissue types. We then re-analyzed a skin and tongue wound healing microarray dataset to see how expression levels of tight junction genes change over time in response to injury. We performed in vitro scratch assays on human oral and skin keratinocyte cell lines to assay for tight junction expression over time, tight junction expression in response to lipopolysaccharide and histamine treatment, and the effects of siRNA knockdown of claudin 1 or occludin on migration and proliferation. Our data showed that oral and skin epithelium expressed different tight junction genes at baseline and during the wound healing response. Knockdown of claudin 1 or occludin led to changes in proliferation and migration in human skin keratinocytes but not oral keratinocytes. Furthermore, we also showed that skin keratinocytes were more permeable than oral keratinocytes upon histamine treatment. In conclusion, this study highlights a specific subset of functional tight junction genes that are differentially expressed between the oral and skin tissues, which may contribute to the mechanisms leading to distinct healing phenotypes in response to injury in the two tissues.

A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

“…F ample, the rate of wound healing and the incidence of scarring are different betwee and epidermal keratinocytes as the healing rate and properties are more effective oral epithelium [112]. Furthermore, keratinocytes from the two sources differ in ce interactions in terms of their expression of tight junctions, which increase epid keratinocyte permeability upon histamine stimulation [113]. Similarly, the secretory tions of epidermal and bronchial keratinocytes can be different according to the tr For example, bronchial keratinocytes can release cytokines in response to bisphe Such an effect has not been illustrated in epidermal keratinocytes [114].…”

Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis

“…However, it has been hypothesized that the differential expression of the tight junctions repertoire in the oral cavity may be involved in the scarring process in this tissue. In a murine model, the expression of claudin 1 and occludin was analyzed and it was concluded that there are genes differentially expressed in oral tissues that can contribute to the mechanisms that lead to the expression of scar phenotypes in response to injuries ( 40 ). Keratin also connects to actin through adherent junctions and desmosomes forming a mechanical unit, while adherent junctions act as mechanosensors in the transduction of mechanical forces between the plasma membrane and the cytoskeleton of actomyosin.…”

Unravelling the therapeutic potential of IL-33 for atrophic AMD

“…1 ). Changes to tight-junction proteins, including ZO-2 and OCLDN, are important in wound-healing responses and RPE barrier integrity and function [ 74 ], and therefore the IL-33-mediated response of mast cell function could influence the outcome in this context. Furthermore, the importance of IL-33 in resolving inflammation is highlighted in a study by Augustine et al that shows following retinal detachment, IL-33 deficient mice display chronic inflammatory responses and increased severity of retinal degeneration [ 68 ].…”