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European Journal of Dentistry May 2024Cells are the building blocks of all living organisms. The presence of cell junctions such as tight junctions, gap junctions, and anchoring junctions between cells play...
Cells are the building blocks of all living organisms. The presence of cell junctions such as tight junctions, gap junctions, and anchoring junctions between cells play a role in cell-to-cell communication in periodontal health and disease. A literature search was done in Scopus, PubMed, and Web of Science to gather information about the effect of cell junctions on periodontal health and disease. The presence of tight junction in the oral cavity helps in cell-to-cell adhesiveness and assists in the barrier function. The gap junctions help in controlling growth and development and in the cell signaling process. The presence of desmosomes and hemidesmosomes as anchoring junctions aid in mechanical strength and tissue integrity. Periodontitis is a biofilm-induced disease leading to the destruction of the supporting structures of the tooth. The structures of the periodontium possess multiple cell junctions that play a significant role in periodontal health and disease as well as periodontal tissue healing. This review article provides an insight into the role of cell junctions in periodontal disease and health, and offers concepts for development of therapeutic strategies through manipulation of cell junctions.
PubMed: 38049123
DOI: 10.1055/s-0043-1775726 -
Cancer Science Jan 2024Plakophilin 3 (PKP3), a component of desmosome, is aberrantly expressed in many kinds of human diseases, especially in cancers. Through direct interaction, PKP3 binds... (Review)
Review
Plakophilin 3 (PKP3), a component of desmosome, is aberrantly expressed in many kinds of human diseases, especially in cancers. Through direct interaction, PKP3 binds with a series of desmosomal proteins, such as desmoglein, desmocollin, plakoglobin, and desmoplakin, to initiate desmosome aggregation, then promotes its stability. As PKP3 is mostly expressed in the skin, loss of PKP3 promotes the development of several skin diseases, such as paraneoplastic pemphigus, pemphigus vulgaris, and hypertrophic scar. Moreover, accumulated clinical data indicate that PKP3 dysregulates in diverse cancers, including breast, ovarian, colon, and lung cancers. Numerous lines of evidence have shown that PKP3 plays important roles in multiple cellular processes during cancer progression, including metastasis, invasion, tumor formation, autophagy, and proliferation. This review examines the diverse functions of PKP3 in regulating tumor formation and development in various types of cancers and summarizes its detailed mechanisms in the occurrence of skin diseases.
Topics: Humans; Desmosomes; Neoplasms; Plakophilins; Skin Diseases
PubMed: 38048779
DOI: 10.1111/cas.16019 -
Journal of Oral and Maxillofacial... 2023Desmosomes are composed of a number of proteins, including cadherins, armadillo proteins and plakoplilins, which are responsible for mediating cell-cell adhesion.... (Review)
Review
Desmosomes are composed of a number of proteins, including cadherins, armadillo proteins and plakoplilins, which are responsible for mediating cell-cell adhesion. Cadherins are transmembrane proteins that bind to each other on adjacent cells, forming a strong adhesive bond between the cells. In normal tissues, desmosomes help to maintain the structural integrity of the tissue by holding the cells together. During carcinogenesis, the structure and function of desmosomes may be altered. For example, in oral cancer, the expression of certain cadherins may be increased, leading to increased cell-cell adhesion and a more cohesive tumour mass. This may contribute to the ability of cancer cells to evade the immune system and resist chemotherapy. In addition to their role in cell adhesion, desmosomes also play a role in cell signaling. The proteins that make up desmosomes can interact with signaling pathways that regulate cell proliferation, migration and survival. Dysregulation of these pathways may contribute to the development and progression of oral cancer. There is also evidence that desmosomes may be involved in the process of invasion and metastasis, which is the spread of cancer cells from the primary tumour to other parts of the body. Cancer cells that have disrupted or abnormal desmosomes may be more likely to migrate and invade other tissues. Overall, desmosomes appear to be important in the development and progression of oral cancer. Further research is needed to fully understand the role of these cell-cell junctions in the disease and to identify potential therapeutic targets.
PubMed: 38033953
DOI: 10.4103/jomfp.jomfp_8_23 -
The keratin-desmosome scaffold of internal epithelia in health and disease - The plot is thickening.Current Opinion in Cell Biology Feb 2024Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the... (Review)
Review
Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the epidermis is well recognized, our review focuses on their emerging importance in internal epithelia. The significance of keratin-desmosome scaffolds (KDSs) in the intestine is highlighted by transgenic mouse models and individuals with inflammatory bowel disease who display profound KDS alterations. In lung, high K8 expression defines a transitional cell subset during regeneration, and K8 variants are associated with idiopathic pulmonary fibrosis. Inherited variants in desmosomal proteins are overrepresented in idiopathic lung fibrosis, and familiar eosinophilic esophagitis. K18 serum fragments are established hepatocellular injury markers that correlate with the extent of histological inflammation. K17 expression is modified in multiple tumors, and K17 levels might be of prognostic relevance. These data should spur further studies on biological roles of these versatile tissue protectors and efforts on their therapeutic targeting.
Topics: Mice; Animals; Keratins; Desmosomes; Cytoskeleton; Epithelium; Intermediate Filaments
PubMed: 38000362
DOI: 10.1016/j.ceb.2023.102282 -
Stem Cell Research Dec 2023Arrhythmogenic cardiomyopathy (ACM) represents the cardiac phenotype of Naxos disease, an autosomal recessive disease with an additional cutaneous phenotype. ACM is...
Arrhythmogenic cardiomyopathy (ACM) represents the cardiac phenotype of Naxos disease, an autosomal recessive disease with an additional cutaneous phenotype. ACM is mainly caused by mutated desmosomal proteins, which are part of cardiac adherens junctions and provide mechanical and electrical stability. Here, we generated a knock-out (KO) of the junctional protein Plakoglobin (JUP-KO; JMUi001-A-4) using the CRISPR/Cas9 system in healthy control induced pluripotent stem cells (iPSCs, (JMUi001-A). JUP-KO iPSCs maintained pluripotency, differentiation potential and genomic integrity and provide an in vitro system modelling ACM when differentiated into cardiomyocytes.
Topics: Humans; Induced Pluripotent Stem Cells; CRISPR-Cas Systems; gamma Catenin; Arrhythmogenic Right Ventricular Dysplasia; Myocytes, Cardiac; Phenotype
PubMed: 37995437
DOI: 10.1016/j.scr.2023.103240 -
Advanced Science (Weinheim,... Feb 2024Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is...
Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient-derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.
Topics: Female; Humans; Breast Neoplasms; Ectopic Gene Expression; Keratins, Hair-Specific; Protein Isoforms
PubMed: 37949677
DOI: 10.1002/advs.202300509 -
BMC Immunology Nov 2023Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has...
BACKGROUND
Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear.
OBJECTIVE
The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera.
METHODS
A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay.
RESULTS
PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation.
CONCLUSION
FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.
Topics: Humans; Pemphigus; Tacrolimus; HSP27 Heat-Shock Proteins; HaCaT Cells; Phosphorylation; Keratinocytes; Desmoglein 3; Immunoglobulin G; Autoantibodies
PubMed: 37940861
DOI: 10.1186/s12865-023-00582-z -
Journal of Animal Science and... Nov 2023The importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations. Sheep...
BACKGROUND
The importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations. Sheep production system is extensive and generally carried out in traditional systems without intensive systematic breeding programmes for high uniform trait production (carcass, wool and milk yield). Therefore, eight indigenous Croatian sheep breeds from eastern Adriatic treated here as metapopulation (EAS), are generally considered as multipurpose breeds (milk, meat and wool), not specialised for a particular type of production, but known for their robustness and resistance to certain environmental conditions. Our objective was to identify genomic regions and genes that exhibit patterns of positive selection signatures, decipher their biological and productive functionality, and provide a "genomic" characterization of EAS adaptation and determine its production type.
RESULTS
We identified positive selection signatures in EAS using several methods based on reduced local variation, linkage disequilibrium and site frequency spectrum (eROHi, iHS, nSL and CLR). Our analyses identified numerous genomic regions and genes (e.g., desmosomal cadherin and desmoglein gene families) associated with environmental adaptation and economically important traits. Most candidate genes were related to meat/production and health/immune response traits, while some of the candidate genes discovered were important for domestication and evolutionary processes (e.g., HOXa gene family and FSIP2). These results were also confirmed by GO and QTL enrichment analysis.
CONCLUSIONS
Our results contribute to a better understanding of the unique adaptive genetic architecture of EAS and define its productive type, ultimately providing a new opportunity for future breeding programmes. At the same time, the numerous genes identified will improve our understanding of ruminant (sheep) robustness and resistance in the harsh and specific Mediterranean environment.
PubMed: 37932811
DOI: 10.1186/s40104-023-00936-y -
Frontiers in Molecular Biosciences 2023Fish gills are not only the respiratory organ, but also essential for ion-regulation, acid-base control, detoxification, waste excretion and host defense. Multifactorial...
Fish gills are not only the respiratory organ, but also essential for ion-regulation, acid-base control, detoxification, waste excretion and host defense. Multifactorial gill diseases are common in farmed Atlantic salmon, and still poorly understood. Understanding gill pathophysiology is of paramount importance, but the sacrifice of large numbers of experimental animals for this purpose should be avoided. Therefore, models, such as cell lines, are urgently required to replace fish trials. An Atlantic salmon gill epithelial cell line, ASG-10, was established at the Norwegian Veterinary institute in 2018. This cell line forms a monolayer expressing cytokeratin, e-cadherin and desmosomes, hallmarks of a functional epithelial barrier. To determine the value of ASG-10 for comparative studies of gill functions, the characterization of ASG-10 was taken one step further by performing functional assays and comparing the cell proteome and transcriptome with those of gills from juvenile freshwater Atlantic salmon. The ASG-10 cell line appear to be a homogenous cell line consisting of epithelial cells, which express tight junction proteins. We demonstrated that ASG-10 forms a barrier, both alone and in co-culture with the Atlantic salmon gill fibroblast cell line ASG-13. ASG-10 cells can phagocytose and express several ATP-binding cassette transport proteins. Additionally, ASG-10 expresses genes involved in biotransformation of xenobiotics and immune responses. Taken together, this study provides an overview of functions that can be studied using ASG-10, which will be an important contribution to gill epithelial research of Atlantic salmon.
PubMed: 37916189
DOI: 10.3389/fmolb.2023.1242879 -
Genes Sep 2023Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to... (Review)
Review
Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to have a strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients to arrhythmic episodes. Variants in one of the five genes ( and ) encoding proteins of the desmosome are known to cause a subset of ACM, which we classify as desmosome-related ACM (dACM). Phenotypically, this disease may lead to sudden cardiac death in young athletes and, during late stages, is often accompanied by myocardial fibrofatty infiltrates. While the pathogenicity of the desmosome genes has been well established through animal studies and limited supplies of primary human cells, these systems have drawbacks that limit their utility and relevance to understanding human disease. Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for modeling ACM in vitro that can overcome these challenges, as they represent a reproducible and scalable source of cardiomyocytes (CMs) that recapitulate patient phenotypes. In this review, we provide an overview of dACM, summarize findings in other model systems linking desmosome proteins with this disease, and provide an up-to-date summary of the work that has been conducted in hiPSC-cardiomyocyte (hiPSC-CM) models of dACM. In the context of the hiPSC-CM model system, we highlight novel findings that have contributed to our understanding of disease and enumerate the limitations, prospects, and directions for research to consider towards future progress.
Topics: Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Cardiomyopathies; Phenotype
PubMed: 37895213
DOI: 10.3390/genes14101864