Pemphigus
Lionel Fry in Atlas of Bullous Diseases, 2020
The primary pathological event in pemphigus is the loss of adhesion of the epidermal cells. The attachment of epidermal cells is mainly through the desmosomes, and to a lesser extent by so-called ‘tight’ or ‘adherence’ junctions. The desmosome is made up of structures called Cadherins which are divided into desmogleins and desmocollins. These structures have an intracellular, a transmembrane and an extracellular component. Intracellularly they are attached to the keratin cytoskeleton and extra-cellularly to that of another cell forming the desmosome (Figure 3.2). Desmogleins are subdivided into desmogleins 1, 2 and 3 and are intracellular components of the desmosome (Figure 3.2). Desmoglein 3 is expressed only in the basal and suprabasal layers of the epidermis, whereas desmoglein 1 is expressed throughout the epidermis but mainly in the upper layers. In mucosae, desmoglein 3 is strongly expressed throughout the epithelium and desmoglein 1 only weakly.
Epithelial Cells
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
A variety of proteins and glycoproteins make up the different portions of the desmosome. Membrane glycoproteins, known as desmogleins or desmocollins, project into the intercellular space to form an intercellular adhesive structure (45). Three desmogleins have been identified (48): desmoglein I has a molecular weight of 150 kD, desmoglein II is a 110–120 kD protein, and desmoglein III is considerably smaller (22 kD). Although desmoglein I is also found in the desmosomal plaque (49), the cytoplasmic side of the desmosome is primarily composed of four nonglycosylated proteins called desmoplakins. Desmoplakins I and II (250 kD and 215 kD, respectively) are somewhat larger proteins than desmoplakins III and IV (83 kD and 78 kD, respectively) (50). Desmin, vimentin, and particularly cytokeratin, make up the tonofilaments (45). Cytokeratin expression is often used as a characteristic feature of epithelial cells.
Introduction to Cell Biology
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Cells that are structurally bound within a tissue must first disassemble their cell-cell contacts to become motile. Between neighboring cells, a number of junctions exist that facilitate adhesion, communication, and structural support. Adherens junctions are supported by the calcium-regulated binding of the extracellular domain of cadherin molecules of adjacent cells. The expression pattern of cadherins is highly specific for different cell types, for example, epithelial cells express E-cadherin and vascular endothelial cells express VE-cadherin. Cadherin molecules are bound by their cytoplasmic domain to β-catenin and via interactions with a-catenin and other actin-binding molecules; the complex is bridged to the actin cytoskeleton. Tight junctions are portions of plasma membrane between adjacent cells that appear to be fused together at points, providing an impermeable barrier to small hydrophilic molecules and ions. Tight junctions also prevent the diffusion of membrane-bound proteins between the apical and basolateral surface; thus they maintain functional polarity. Gap junctions are small pores between adjacent cells that allow for diffusion of small molecules and ions. Finally, desmosomes comprise specific cadherins known as desmoglein and desmocollin that are bound to intermediate filaments via the cytosolic plakoglobin and desmoplakins, providing mechanical strength. Likewise, intermediate filament bundles secure adhesion to the extracellular matrix through structures called hemidesmosomes.
Optimization of an oral mucosa in vitro model based on cell line TR146
Published in Tissue Barriers, 2020
Grace C. Lin, Tamara Leitgeb, Alexandra Vladetic, Heinz-Peter Friedl, Nadine Rhodes, Angela Rossi, Eva Roblegg, Winfried Neuhaus
In order to confirm the presence of continuous tight junctions, the localization of tight junction marker occludin was morphologically characterized using immunofluorescent staining on microscope slides (see supplementary Figure S4A). To confirm the presence of cytokeratins, differentiation markers for epithelial cells, at the protein level additionally to the mRNA level, immunofluorescent staining (K5/K8) was accomplished on microscope slides and inserts (see supplementary Figure S4A-B). In general, HE stainings showed a stratified non-keratinized epithelium, which corresponds to the phenotype of the cell line of the buccal region. Interestingly, the cornification markers (loricrin > filaggrin > involucrin) showed a high upregulation under the presence of hydrocortisone or other supplement compositions containing hydrocortisone such as HKGS and HKGS/KGF/A2P. This confirmed the enhanced differentiation upon hydrocortisone in epithelial cell layers, which was in concordance to higher TEER values of the accordingly treated TR146 inserts. In the oral epithelium, desmosomes play a pivotal role as intercellular junctions.51 Although one focus of the presented study is the comprehensive investigation of the expression of tight junction proteins, the expression of desmoglein 3, a desmosome formation facilitating protein, was evaluated with conventional qPCR (see supplementary Figure S5). Interestingly, DMEM media supplemented with 1000 nM hydrocortisone, HKGS (the optimized media) and with HKGS/KGF/A2P showed an upregulation to a similar scale compared to the biopsy samples of healthy donors.
The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung
Published in Upsala Journal of Medical Sciences, 2020
Inmaculada Galindo, Mercedes Gómez-Morales, Inés Díaz-Cano, Álvaro Andrades, Mercedes Caba-Molina, María Teresa Miranda-León, Pedro Pablo Medina, Joel Martín-Padron, María Esther Fárez-Vidal
Desmoglein 3 (DSG3) is one of seven desmosomal cadherins. Desmosomal proteins act as tumour suppressors and are downregulated in epithelial–mesenchymal transition and in tumour cell invasion and metastasis. However, some studies have shown the upregulation of several desmosomal components in cancer, including DSG3, and overexpression of these proteins has been related to the prognosis. Therefore, desmosomal proteins can potentially serve as diagnostic and prognostic markers (22). Keratin 15 (KRT15) is a type I keratin protein present in the basal keratinocytes of stratified epithelium. For this reason, it has been reported as a marker of stem cells. However, several studies have demonstrated KRT15 expression in differentiated cells (23). Our group previously reported that gene sequences corresponding to the desmosomal plaque-related proteins PKP1, DSG3, and KRT15 were differentially expressed in primary AC and SCC of the lung (24). Subsequently, we also described the localization of PKP1 in nucleus, cytoplasm, and cell membrane in tumours and proposed the utilization of these proteins as immunohistochemical markers (25).
CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy
Published in OncoImmunology, 2018
Sadia Zafar, Suvi Sorsa, Mikko Siurala, Otto Hemminki, Riikka Havunen, Victor Cervera-Carrascon, João Manuel Santos, Hongjie Wang, Andre Lieber, Tanja De Gruijl, Anna Kanerva, Akseli Hemminki
Oncolytic adenoviruses are an attractive platform for cancer immunotherapy due to their tumor-specific replication, ability to infect different tumors, good stability in vivo, and favorable safety profile in humans.60,61 In this study, we studied CD40L-armed adenovirus serotype 3 Ad3-hTERT-CMV-hCD40L. It features the following important aspects: fully serotype 3 to enhance tumor transduction through the intravenous route, tumor selectivity due to the presence of hTERT promoter, and induction of apoptosis in CD40+ tumors.36 As discussed before, the serotype 3 platform may be advantageous to the ubiquitous Ad5 in several ways.25–36 The primary receptor for Ad3, desmoglein-2, is highly expressed in advanced tumors,25–36 allowing enhanced tumor transduction. Moreover, it has been reported that fully Ad3 capsid allows effective intravenous delivery in animals and humans.25–36