Making sense of the epithelial barrier: What molecular biology and genetics tell us about the functions of oral mucosal and epidermal tissues

Department of Oral Biology, School of Dentistry, University of Washington, Seattle 98195-7132, USA.
Journal of dental education (Impact Factor: 0.97). 05/2002; 66(4):564-74.
Source: PubMed


The epidermis of skin and the oral mucosa are highly specialized stratified epithelia that function to protect the body from physical and chemical damage, infection, dehydration, and heat loss. To maintain this critical barrier, epithelial tissues undergo constant renewal and repair. Epithelial cells (keratinocytes) undergo a program of terminal differentiation, expressing a set of structural proteins, keratins, which assemble into filaments and function to maintain cell and tissue integrity. Two types of cell adhesion structures, desmosomes and hemidesmosomes, function to glue keratinocytes to one another and to the basement membrane, and connect the keratin cytoskeleton to the cell surface. Keratinizing epithelia such as the epidermis and oral gingiva that have to withstand severe physical and chemical forces produce a toughened structure, the cornified cell envelope. This envelope is a major component of the epithelial barrier at the tissue surface. This article summarizes our current understanding of the structure and function of these different cellular components and discusses various genetic and acquired diseases that alter tissue integrity and barrier function. We also highlight recent work demonstrating how loss or attenuation of certain proteases can lead to early onset periodontitis and tooth loss as well as other epithelial abnormalities.

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Available from: Richard Jurevic
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    • "Histological sections of healthy human skin confirm HYAL1 signal is prominent in the granular layer, whilst HA mostly surrounds basal and spinous keratinocytes. HYAL1 cannot be detected in oral mucosal epithelium (Figure 1f) which lacks a granular layer (Presland and Jurevic, 2002). HYAL1 activity is also clearly demonstrated using zymographic analysis of human epidermis extracts (Figure 1g). "
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    ABSTRACT: Abbreviations: HA, hyaluronan; HAS, hyaluronan synthase; HYAL, hyaluronidase; RHE, reconstructed human epidermis; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; TEER, trans-epithelial electric resistance; WT, wild-type
    Full-text · Article · Jul 2015 · Journal of Investigative Dermatology
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    • "Keratinized oral epithelia found on the palate and gingiva express keratin-1 and -10 in the spinous layer, which are markers of well-differentiated cornified epithelial cells [2]. The cornified epithelium contributes to the barrier provided by gingival epithelium [3]. Gingival epithelial cells come into contact with a variety of bacteria. "
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    ABSTRACT: P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingival epithelial cells were challenged and barrier function was examined by fluorescent dextran and apoptosis was measured by cytoplasmic histone associated DNA. Gene expression levels were measured by real-time PCR with and without FOXO1 and FOXO3 siRNA compared to scrambled siRNA. P. gingivalis induced a loss of barrier function and stimulated gingival epithelial cell apoptosis in multilayer cultures that was in part gingipain dependent. P. gingivalis stimulated an increase in FOXO1 and FOXO3 mRNA, enhanced mRNA levels of genes associated with differentiated keratinocyte function (keratin-1, -10, -14, and involucrin), increased mRNA levels of apoptotic genes (BID and TRADD), reduced mRNA levels of genes that regulate inflammation (TLR-2 and -4) and reduced those associated with barrier function (integrin beta-1, -3 and -6). The ability of P. gingivalis to modulate these genes was predominantly FOXO1 and FOXO3 dependent. The results indicate that P. gingivalis has pronounced effects on gingival keratinocytes and modulates mRNA levels of genes that affect host response, differentiation, apoptosis and barrier function. Moreover, this modulation is dependent upon the transcription factors FOXO1 or FOXO3. In addition, a new function for FOXO1 was identified, that of suppressing TLR-2 and TLR-4 and maintaining integrin beta -1, beta -3 and beta -6 basal mRNA levels in keratinocytes.
    Full-text · Article · Nov 2013 · PLoS ONE
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    • "While desmosomes and AJs mediate intercellular adhesion in most layers of the oral epithelium (Mahoney et al., 2006; Niessen, 2007), mature TJs expressing occludin are confined to the upper spinous and granular epithelial layers, where they strictly control the paracellular transit of chemicals and pathogens (Niessen, 2007). Altogether, these intercellular junctions are needed for the preservation of the epithelial integrity and the barrier function of the normal oral mucosa against dehydration and a huge variety of external stresses (Presland & Jurevic, 2002). A potent external injury, such as cigarette smoke, may determine a degenerative domino effect that involves both keratinocyte intercellular adhesion and TD because of the reciprocal link in normal human oral mucosa. "
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    ABSTRACT: Human oral mucosa is the combustion chamber of cigarette, but scanty evidence is available about the early smoke effects. The present work aimed at evaluating from a morphological point of view whole smoke early effects on epithelial intercellular adhesion and keratinocyte terminal differentiation in a three-dimensional model of human oral mucosa. Biopsies of keratinized oral mucosa of healthy nonsmoking women (n = 5) were collected. After culturing in a Transwell system, one fragment of each biopsy was exposed to the smoke of one single cigarette; the remnant represented the internal control. The distribution of epithelial differentiation markers (keratin-10, K10, and keratin-14, K14, for suprabasal and basal cells respectively), desmosomes (desmoglein-1, desmoglein-3), tight junctions (occludin), adherens junctions (E-cadherin, β-catenin), and apoptotic cells (p53, caspase 3) were evaluated by immunofluorescence. Quantitative analysis of K14 immunolabeling revealed an overexpression in the suprabasal layers as early as 3 h after smoke exposure, without impairment of the epithelial junctional apparatus and apoptosis induction. These results suggested that the first significant response to cigarette smoke came from the basal and suprabasal layers of the human oral epithelium. The considered model maintained the three-dimensional arrangement of the human mucosa in the oral cavity and mimicked the inhalation/exhalation cycle during the exposure to cigarette smoke, offering a good possibility to extrapolate the reported observations to humans.
    Full-text · Article · May 2012 · Inhalation Toxicology
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