Immortalized Human hTert/KER-CT Keratinocytes a Model System for Research on Desmosomal Adhesion and Pathogenesis of Pemphigus Vulgaris

Pemphigus Vulgaris is an autoimmune disease that results in blister formation in the epidermis and in mucosal tissues due to antibodies recognizing desmosomal cadherins, mainly desmoglein-3 and -1. Studies on the molecular mechanisms of Pemphigus have mainly been carried out using the spontaneously...

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Veröffentlicht in:International journal of molecular sciences 2019-06, Vol.20 (13), p.3113
Hauptverfasser: Beckert, Benedikt, Panico, Francesca, Pollmann, Robert, Eming, Rüdiger, Banning, Antje, Tikkanen, Ritva
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container_title International journal of molecular sciences
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creator Beckert, Benedikt
Panico, Francesca
Pollmann, Robert
Eming, Rüdiger
Banning, Antje
Tikkanen, Ritva
description Pemphigus Vulgaris is an autoimmune disease that results in blister formation in the epidermis and in mucosal tissues due to antibodies recognizing desmosomal cadherins, mainly desmoglein-3 and -1. Studies on the molecular mechanisms of Pemphigus have mainly been carried out using the spontaneously immortalized human keratinocyte cell line HaCaT or in primary keratinocytes. However, both cell systems have suboptimal features, with HaCaT cells exhibiting a large number of chromosomal aberrations and mutated p53 tumor suppressor, whereas primary keratinocytes are short-lived, heterogeneous and not susceptible to genetic modifications due to their restricted life-span. We have here tested the suitability of the commercially available human keratinocyte cell line hTert/KER-CT as a model system for research on epidermal cell adhesion and Pemphigus pathomechanisms. We here show that hTert cells exhibit a calcium dependent expression of desmosomal cadherins and are well suitable for typical assays used for studies on Pemphigus, such as sequential detergent extraction and Dispase-based dissociation assay. Treatment with Pemphigus auto-antibodies results in loss of monolayer integrity and altered localization of desmoglein-3, as well as loss of colocalization with flotillin-2. Our findings demonstrate that hTert cells are well suitable for studies on epidermal cell adhesion and Pemphigus pathomechanisms.
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source MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Autoantibodies - immunology
Autoimmune diseases
Biomarkers
Calcium
Cell Adhesion
Cell adhesion & migration
Cell differentiation
Cell Line
Cell Line, Transformed
Chromosome aberrations
Chromosomes
CRISPR
Cyclin-dependent kinase 4
Desmosomes - genetics
Desmosomes - immunology
Desmosomes - metabolism
Differentiation
Experiments
Fluorescent Antibody Technique
Gene Expression
Genomes
Genotypes
Humans
Keratinocytes
Keratinocytes - immunology
Keratinocytes - metabolism
Medical research
Models, Biological
Mutation
Pathogenesis
Pemphigus
Pemphigus - etiology
Pemphigus - metabolism
Pemphigus - pathology
Proteins
Skin diseases
Telomerase
Telomerase - genetics
Telomerase reverse transcriptase
title Immortalized Human hTert/KER-CT Keratinocytes a Model System for Research on Desmosomal Adhesion and Pathogenesis of Pemphigus Vulgaris
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