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Anais Brasileiros de Dermatologia Jul 2019Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and...
Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.
Topics: Adult; Autoantibodies; Desmosomes; Diagnosis, Differential; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Male; Middle Aged; Pemphigus; Skin; Surveys and Questionnaires
PubMed: 31365654
DOI: 10.1590/abd1806-4841.20199011 -
Cold Spring Harbor Perspectives in... Apr 2018Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell... (Review)
Review
Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell proliferation, and migration. Defects in cell-cell junctions give rise to a wide range of tissue abnormalities that disrupt homeostasis and are common in genetic abnormalities and cancers. Here, we discuss the organization and function of cell-cell junctions primarily involved in adhesion (tight junction, adherens junction, and desmosomes) in two different epithelial tissues: a simple epithelium (intestine) and a stratified epithelium (epidermis). Studies in these tissues reveal similarities and differences in the organization and functions of different cell-cell junctions that meet the requirements for the specialized functions of each tissue. We discuss cell-cell junction responses to genetic and environmental perturbations that provide further insights into their roles in maintaining tissue homeostasis.
Topics: Adherens Junctions; Animals; Cell Movement; Cell Proliferation; Desmosomes; Epithelial Cells; Epithelium; Homeostasis; Humans; Intercellular Junctions; Intestinal Mucosa; Signal Transduction; Tight Junctions; Wound Healing
PubMed: 28600395
DOI: 10.1101/cshperspect.a029181 -
The Journal of Allergy and Clinical... Apr 2020Autoimmune bullous skin diseases, such as pemphigus and pemphigoid, may enable clarification of the mechanisms of immune regulation in the skin. Pemphigus and pemphigoid... (Review)
Review
Autoimmune bullous skin diseases, such as pemphigus and pemphigoid, may enable clarification of the mechanisms of immune regulation in the skin. Pemphigus and pemphigoid are mediated by essentially IgG autoantibodies against structural proteins of the desmosomes at cell-cell junctions and hemidesmosomes at epidermal-dermal junctions, respectively, and are characterized by blisters and erosions in the skin and/or mucous membranes. Intensive investigation over the last 3 decades has identified their target antigens and developed serological diagnostic tools as well as mouse models to help us understand their pathophysiology. Based on these advances, several new therapeutic approaches have become available, and more effective and less toxic targeted approaches are under development.
Topics: Animals; Antigen-Antibody Complex; Autoantibodies; Autoimmune Diseases; Desmosomes; Disease Models, Animal; Humans; Mice; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pemphigus; Serology; Skin; Skin Diseases, Vesiculobullous
PubMed: 32272980
DOI: 10.1016/j.jaci.2020.02.013 -
Journal of Veterinary Cardiology : the... Apr 2022Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease seen in dogs, cats, and humans. A common entity in Boxers and the related...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease seen in dogs, cats, and humans. A common entity in Boxers and the related English bulldog, the disease is characterized by fatty or fibrofatty replacement of the myocardium, ventricular arrhythmias, and the potential for syncope or sudden death. In some individuals, concomitant left ventricular involvement results in systolic dysfunction and a progression to congestive heart failure. The clinical and pathological characteristics of ARVC share many similarities in dogs and humans, and Boxers serve as an important spontaneous model of the disease. Although multiple mechanisms have been implicated in the pathogenesis of ARVC, the disease is ultimately considered to be a disorder of the desmosome. Multiple causal genetic mutations have been identified in people, and over 50% of affected humans have an identifiable mutation in desmosomal proteins. To date, only a single genetic mutation has been associated with ARVC in Boxer dogs. Other as-yet-undiscovered genetic mutations and epigenetic modifiers of the disease are likely. Treatment of ARVC in dogs is focused on controlling ventricular arrhythmias and associated clinical signs. This article will review the pathophysiology, clinical diagnosis, treatment, and prognosis of ARVC in the dog.
Topics: Animals; Arrhythmias, Cardiac; Arrhythmogenic Right Ventricular Dysplasia; Dog Diseases; Dogs; Heart Failure; Humans; Myocardium
PubMed: 34503916
DOI: 10.1016/j.jvc.2021.07.001 -
Science (New York, N.Y.) Feb 2016Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise...
Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.
Topics: Aged; Aging; Alopecia; Animals; Autoantigens; Cell Differentiation; Cellular Senescence; DNA Damage; Desmosomes; Female; Genomic Instability; Hair Follicle; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Non-Fibrillar Collagens; Proteolysis; Stem Cells; Collagen Type XVII
PubMed: 26912707
DOI: 10.1126/science.aad4395 -
European Cells & Materials Aug 2019Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching... (Review)
Review
Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching the underlying soft tissues and bone, which in turn can lead to inflammation and subsequent bone resorption. The present review investigated oral wound closure and the role of micro-environment, saliva, crevicular fluid and microbiota in wound healing. The importance of the junctional epithelium (peri-implant epithelium) attachment to the abutment surface was investigated. Current research focuses on macro-design, surface-topography, surface-chemistry, materials, coatings and wettability to enhance attachment, since these optimised surface properties are expected to promote keratinocyte attachment and spreading through hemi-desmosome formation. Detailed studies describing the extent of junctional epithelium attachment - e.g. barrier function, hemi-desmosomes, epithelium quality, composition of the external basement membrane or ability of the epithelium to resist microbial penetration and colonisation - are not yet reported in animals due to ethical considerations, scalability, expense, technical challenges and limited availability of antibodies. In vitro studies generally include relatively simple 2D culture models, which lack the complexity required to draw relevant conclusions. Additionally, human organotypic 3D mucosa models are being developed. The present review concluded that more research using these organotypic mucosa models may identify relevant parameters involved in soft-tissue-abutment interactions, which could be used to study different macro-shapes and surface modifications. Such studies would bridge the gap between clinical, animal and traditional in vitro cell culture studies supporting development of abutments aiming at improved clinical performance.
Topics: Animals; Cell Adhesion; Dental Abutments; Epithelial Cells; Gingiva; Humans; Wound Healing
PubMed: 31410840
DOI: 10.22203/eCM.v038a06 -
Annual Review of Pathology Jan 2018Tissue integrity is crucial for maintaining the homeostasis of living organisms. Abnormalities that affect sites of cell-cell contact can cause a variety of debilitating... (Review)
Review
Tissue integrity is crucial for maintaining the homeostasis of living organisms. Abnormalities that affect sites of cell-cell contact can cause a variety of debilitating disorders. The desmosome is an essential cell-cell junctional protein complex in tissues that undergo stress, and it orchestrates intracellular signal transduction. Desmosome assembly and junctional integrity are required to maintain the overall homeostasis of a tissue, organ, and organism. This review discusses the desmosome and the human diseases associated with its disruption.
Topics: Desmosomes; Humans
PubMed: 29414250
DOI: 10.1146/annurev-pathol-020117-044030 -
Cell and Tissue Research Jun 2015Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement... (Review)
Review
Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement integrates adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, which occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on the way in which human diseases can inform our understanding of basic desmosome biology and in turn, the means by which fundamental advances in the cell biology of desmosomes might lead to new treatments for acquired diseases of the desmosome.
Topics: Animals; Desmosomes; Humans; Models, Biological; Skin Diseases
PubMed: 25795143
DOI: 10.1007/s00441-015-2155-2 -
Advances in Experimental Medicine and... 2016Telocyte, different to fibroblast and dendritic cell, is a novel type of interstitial cell, whose key features are their smaller cell body with very long prolongations... (Review)
Review
Telocyte, different to fibroblast and dendritic cell, is a novel type of interstitial cell, whose key features are their smaller cell body with very long prolongations of uneven caliber, termed telopodes. The telocytes have been continuously discovered to be present in many tissues and organs. Whether telocytes exist in the blood and vascular wall is not clear. Our research group, for the first time, testified that telocytes also exist in the blood and large sized arterial and venous wall under scanning and transmission electron microscope. In static condition, blood telocytes and their prolongations usually attach on endothelial surface. We speculate that the blood telocyte maybe come from the bone marrow, because most of formed element in the blood originated from bone marrow. The telocytes within arterial wall locate in the tunica adventitia and close to outer elastic lamina. And, the telocytes in venous wall commonly situate in the subendothelial layer. The morphological features of blood and vascular telocytes are consistent with the telocytes in other organs and tissues. Their real function of telocytes in cardiovascular system preserved to be further investigated.
Topics: Animals; Arteries; Capillaries; Cell Communication; Desmosomes; Endothelial Cells; Fibroblasts; Humans; Macrophages; Mice; Microscopy, Electron, Transmission; Swine; Telocytes; Veins
PubMed: 27796900
DOI: 10.1007/978-981-10-1061-3_24 -
Molecular Carcinogenesis Jun 2024Plakophilin 1 (PKP1) belongs to the desmosome family as an anchoring junction protein in cellular junctions. It localizes at the interface of the cell membrane and... (Review)
Review
Plakophilin 1 (PKP1) belongs to the desmosome family as an anchoring junction protein in cellular junctions. It localizes at the interface of the cell membrane and cytoplasm. Although PKP1 is a non-transmembrane protein, it may become associated with the cell membrane via transmembrane proteins such as desmocollins and desmogleins. Homozygous deletion of PKP1 results in ectodermal dysplasia-skin fragility syndrome (EDSF) and complete knockout of PKP1 in mice produces comparable symptoms to EDSF in humans, although mice do not survive more than 24 h. PKP1 is not limited to expression in desmosomal structures, but is rather widely expressed in cytoplasm and nucleus, where it assumes important cellular functions. This review will summarize distinct roles of PKP1 in the cell membrane, cytoplasm, and nucleus with an overview of relevant studies on its function in diverse types of cancer.
PubMed: 38888207
DOI: 10.1002/mc.23779